2011年 · 第124卷第17期

INTRODUCTION

Abstract：The treatment of gliomas is highly individualized.Surgery for gliomas is essentially for histological diagnosis,to alleviate mass effect,and most importantly,to favor longer survival expectancy.During the past two decades,many surgical techniques and adjuvants have been applied to glioma surgery in China,which lead to a rapid development in the field of cerebral glioma surgery.This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China.A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China.The following databases were searched:the Pubmed (January 1995 to date);China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date).A selection criterion was established to exclude duplicates and irrelevant studies.The outcome measures were extracted from included studies.A total of 3307 articles were initially searched.After excluded by abstracts and full texts,69 studies conducted in the mainland of China were included and went through further analysis.The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change.Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients.The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention.The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient。

Abstract：Background Everlasting cellular proliferation is the fundamental feature during gliomagenesis and Ki-67 is one of the classical proliferation markers in human glioblastoma multiforme (GBM).However,the driver genes or core pathways for cellular proliferation in GBM have not been elucidated systematically.Methods We evaluated by immunohistochemistry the prognostic value of Ki-67 expression in the clinical outcome of 156 Chinese patients with GBM and a total of 64 GBM samples were selected for further Agilent genome-wide microarray analysis.On the basis of the microarray data from Tiantan (n=64) and The Cancer Genome Atlas (TCGA) (n=202)database,differentially expressed genes between the GBM subgroups with high or low level of Ki-67 expression were identified using Significance Analysis of Microarrays (SAM).Gene Ontology (GO) and KEGG Pathway analyses were then undertaken for the Ki-67 associated genes to identify the most significant biological processes and signaling pathways.Results We confirmed that Ki-67 was an independent prognostic indicator in the largest Chinese patient cohort of 156 GBM samples via immunohistochemical staining.Survival analysis of Ki-67 over-expression revealed a highly significant association with a worse clinical outcome (P=0.010 for progression-free survival;P=0.007 for overall survival).Comparative and integrated analysis between Tiantan and TCGA database identified a 247-gene "proliferation signature"(205 up-regulated and 42 down-regulated genes) that distinguished Ki-67 expression phenotypes.GO and KEGG Pathway analyses further indicated that Ki-67 expression phenotype was associated with distinct changes in gene expression associated with the regulation of cellular growth and proliferation.Conclusions Proliferation marker Ki-67 is an independent prognostic indicator in Chinese GBM patients.And Ki-67 associated proliferation signature identified through genome-wide microarray analysis may provide potential targets for anti-proliferation therapy in GBM。

Abstract：Background Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults.Magnetic resonance imaging (MRI) is routinely used in the diagnosis,characterization and clinical management of GBM.The diagnosis and treatment of GBM is largely guided by histopathology and immunohistochemistry.This study aimed to identify the relationship between magnetic resonance features and molecular pathology of GBM.Methods MRI images of 43 glioblastoma patients were collected.Four imaging features,degree of edema,contrast tumor enhanced/T2 ratio,multiple lesions and tumor across the midline,were selected to identify their relationship with P53,Ki-67 and O6-methylguanine-DNA methltransferase (MGMT) expression in patients with GBM.The relationship between imaging features and molecular pathology was studied by chi-square test using the software SPSS 13.0.Results High expression of P53 was found correlated with low contrast tumor enhanced/T2 ratio,low expression of Ki-67 was correlated with multiple lesions and high expression of KI-67 may be related with tumor across the midline,low expression of MGMT was correlated with edema.Conclusion Some MRI features such as the degree of edema,contrast tumor enhanced/T2 ratio,multiple lesions and tumor acrossing the midline are correlated with P53,Ki-67 and MGMT of GBM。

Abstract：Background Our previous study had cloned two glioma cell lines SWOZ1 and SWOZ2 isolated from parental glioma cell line SWO38.The 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance of SWOZ1 was higher than that of SWOZ2.Since O6-methylguanine-DNA methyltransferase (MGMT) was thought to be closely related to BCNU resistance in glioma,this study aimed to explore the function of MGMT in glioma resistant to BCNU.Methods A BCNU resistant glioma cell line SWOZ2-BCNU was established.The expression of MGMT was detected in SWOZ1,SWOZ2 and SWOZ2-BCNU.Small interferencing RNA targeting MGMT was used to silence the expression of MGMT in resistant cell lines SWOZ1 and SWOZ2-BCNU.The cytotoxicity of BCNU to these cells was measured using the cell counting kit-8 assay.Statistical analysis was carried out by one-way analysis of variance in statistical package SPSS 13.0.Results The resistance of SWOZ1 and SWOZ2-BCNU against BCNU was 4.9-fold and 5.3-fold higher than that of SWOZ2.The results of quantitative RT-PCR and Western blotting confirmed that MGMT was both significantly increased in SWOZ1 and SWOZ2-BCNU compared to SOWZ2.After transfection with small interferencing RNA targeting MGMT,a decreased level of MGMT mRNA expression in SWOZ1 and SWOZ2-BCNU for more than 75% compared to negative control was found and confirmed by Western blotting.As a result,the resistance against BCNU was reversed for about 50% both in the BCNU-resistant cell lines SWOZ1 and SWOZ2-BCNU.Conclusions Silencing MGMT with specific small interferencing RNA can reverse the BCNU resistant phenotype in these glioma cell lines.MGMT may play an important role both in intrinsic and acquired BCNU-resistance in glioma。

Abstract：Background Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT),consequently reducing the production of α-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway.However,given that the roles of other active sites in IDH1 substrate binding remain unclear,we aimed to investigate IDH1 mutation pattern and its influence on enzyme function.Methods Fifteen IDH1 catalytic active site candidates were selected for in silico mutagenesis and protein homology modeling.Binding free energy of the IDH1/ICT complexes with single-site mutations was compared with that of the wild type.The affinity of 10 IDH1 catalytic active sites for the ICT substrate was further calculated.Results The IDH1 active site included seven residues from chain A (A77Thr,A94Ser,A100Arg,A132Arg,A1O9Arg,A275Asp,and A279Asp) and three residues from chain B (B214Thr,B212Lys,and B252Asp) that constituted the substrate ICT-binding site.These residues were located within 0.5 nm of ICT,indicating a potential interaction with the substrate.IDH1 changes of binding free energy (△E) suggested that the A132Arg residue from chain A contributes three hydrogen bonds to the ICT α-carboxyl and β-carboxyl groups,while the other nine residues involved in ICT binding form only one or two hydrogen bonds.Amino acid substitutes at A132Arg,A109Arg,and B212Lys sites,had the greatest effect on enzyme affinity for its substrate.Conclusions Mutations at sites A132Arg,A109Arg,and B212Lys reduced IDH1 affinity for ICT,indicating these active sites may play a central role in substrate binding.Mutations at sites A77Thr,A94Ser,and A275Asp increased the affinity of IDH1 for ICT,which may enhance IDN1 catalytic activity.Mutant IDH1 proteins with higher catalytic activity than the wild-type IDH1 could potentially be used as a novel gene therapy for glioblastoma multiforme。

Abstract：Background Invasion growth is the most characteristic biological phenotype of glioblastoma,but the molecular mechanism in glioma cell invasion is poorly understood.Recent data have showed that microRNA plays an essential role in tumor invasion.Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion.Methods Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR-7 mimics in U87 and U251 cells.Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7.The levels of miR-7,matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay,and the levels of FAK,MMP-2,MMP-9,total and phosphorylation serine/threonine kinase (AKT),and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis.Results Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells.And up-regulation of miR-7 reduced FAK protein expression,Further,luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA.In addition,miR-7 repressed p-ERK1/2 and p-AKT level,MMP-2 and MMP-9 expression.Finally,the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues.Conclusion To our knowledge,these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention。

Abstract：Background Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity.Hippocampal neurons are abundant in glucocorticoid receptor,and there is significant change in GR expression under certain pathological state.Epilepsy is a special pathological state of the central nervous system.This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model.Methods Firstly,we established the basolateral amygdale-electrical kindled rat epilepsy model.Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment.In addition,the processes of epileptic seizures were observed and electroencephalograms were recorded.One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups,followed Fisher's least significant difference (LSD) for paired comparison.Results The rats were successfully kindled after an average of (13.50±3.99) times electrical stimulation,in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P＜0.001).The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P ＜0.001 compared with the epilepsy group),accompanied by attenuation of seizures and improvement of electroencephalograms.Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling.Anti-epilepsy drugs exposure can retard this change。

Abstract：Background Recently,1,5-dicaffeoylquinic acid (1,5-DQA),a caffeoylquinic acid derivative isolated from Aster scaber,was found to have neuroprotective effects.However,the protective mechanisms of 1,5-DQA have not yet been clearly identified.The purpose of this study was to explore the protective mechanisms of 1,5-DQA on neuronal culture.Methods We investigated the neuroprotective effects of 1,5-DQA against amyloid β1-42 (Aβ42)-induced neurotoxicity in primary neuronal culture.To evaluate the neuroprotective effects of 1,5-DQA,primary cultured cortical neurons from neonate rats were pretreated with 1,5-DQA for 2 hours and then treated with 40 μmol/L Aβ42 for 6 hours.Cell counting kit-8,Hoechst staining and Western blotting were used for detecting the protective mechanism.Comparisons between two groups were evaluated by independent t test,and multiple comparisons were analyzed by one-way analysis of variance (ANOVA).Results 1,5-DQA treated neurons showed increased neuronal cell viability against Aβ42 toxicity in a concentration-dependent manner,both phosphoinositide 3-kinase (P13K)/Akt and extracellular regulated protein kinase 1/2 (Erk1/2)were activated by 1,5-DQA with stimulating their upstream tyrosine kinase A (Trk A).However,the neuroprotective effects of 1,5-DQA were blocked by LY294002,a PI3K inhibitor,but not by PD98059,an inhibitor of mitogen-activated protein kinase kinase.Furthermore,1,5-DQA's anti-apoptotic potential was related to the enhanced inactivating phosphorylation of glycogen synthase kinase 3β (GSK3β) and the modulation of expression of apoptosis-related protein Bcl-2/Bax.Conclusion These results suggest that 1,5-DQA prevents Aβ42-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A,then the inhibition of GSK3β as well as the modulation of Bcl-2/Bax。

Abstract：Background Adipose-derived stromal cell (ADSC) differentiation into neural cells in vitro is becoming widely studied.However,there are few reports on astrocytes following differentiation,and particularly on maturation and electrophysiology.In this study,we used various methods to determine ADSC-derived astrocyte maturity.Methods Chemical induction with isobutylmethylxanthine (IBMX) was used to differentiate adult ADSCs into astrocytes followed by hematoxylin-eosin (HE) staining to observe morphology and transmission electron microscopy for cellular ultrastructure assessment.Immunofluorescence was used to detect expression of neural stem cell marker nestin as well as glial markers glial fibrillary acidic protein (GFAP) and S-100.In addition,we measured membrane potentials in bis-(1,3-dibarbituric acid) trimethine oxanol-labeled ADSCs and astrocytes by stimulation with a high potassium solution under an inverted fluorescence microscope.Finally,cell cycle distribution was detected by flow cytometry.Results Typical astrocyte morphology was shown by HE staining after 48-hour differentiation.Glial fibril was observed with transmission electron microscopy.GFAP and S-100 were not expressed in the control group,but were expressed within 24-hour differentiation and reached a maximum at day 14 with no change up to day 28.Nestin was weakly expressed in control cells and also reached a maximum at day 14 with the percentage of positive cells constant until day 21 followed by a decrease.Differentiated cell membrane potentials after stimulation with potassium were slightly increased,and then gradually declined over time.There was no significant membrane potential change in the control group.Flow cytometry showed that the percentage of cells in G0/G1 phase was 93% and only 5% in S phase.Conclusion ADSCs were differentiated into mature astrocytes with typical characteristics including morphology,uitrastructure,marker protein expression,mature potassium channels and mitotic capacity。

Abstract：Background Although the first leading cause of death in China was malignant neoplasms (mortality,374.1 per 100000 person-years),the full impact of primary brain tumors (PBT) on the healthcare system is not completely described because there are a few well documented reports about the epidemiologic features of brain tumors.This study aimed to report a comprehensive assessment on the prevalence of PBT.Methods A multicenter cross-sectional study on brain tumor (MCSBT) in China was initiated in five regional centers:Daqing (northeast),Puyang (north of China),Shiyan (center of China),Ma'anshan (center of China) and Shanghai (southeast).Prevalence rate was calculated by counting the number of people living with a PBT between October 1,2005 and September 30,2006 and dividing by the total population of the five communities at January 1,2006.Estimates of prevalence were expressed as percentages and grouped according to gender and to age in fifteen-year categories.Within these strata,the rates were estimated with 95% confidence intervals (C/) using the accurate calculation of CI for Poisson distribution.A chi-square test was used to compare the various frequencies with α＜0.05.Age-standardized prevalence with the direct method was calculated with the ten-year age-specific prevalence and the age distribution of the Chinese population in 2010,obtained from Worldpopulation prospects:the 2008 revision.Results We estimated that the overall prevalence of PBT was 24.56 per 100 000 (95% CI,14.85 to 34.27),and the overall prevalence of PBT in female population (30.57 per 100 000 and its 95% CI ranged from 19.73 to 41.41 ) was higher than that in male population (18.84 per 100 000 and its 95% CI ranged from 10.33 to 27.35).However,the discrepancy between genders was not statistically significant because the 95% CI overlapped.Of 272 cases of newly diagnosed PBT,the proportion of histological subtypes by age groups,gender was statistically different (χ2=52.6510,P <0.0001).More than half of all reported tumors (52.57%) were either gliomas or meningiomas.For the youngest (aged from 0-19)strata of the population,glioma appeared to occur more than other subtypes,accounting for 55.56% of all of cases.The majority of brain tumors presented in those aged from 20 to 59 years was pituitary adenomas (45.12%) and gliomas (31.10%).Opposed to brain tumors in adults and teenage,gliomas only accounted for 22.22%.Meanwhile,the median ages at diagnosis of the patients with PBT were similar between males and females except for pituitary adenomas (male: 59 years old; female: 45 years old).Conclusions Age standardized prevalence of PBT is 22.52 per 100 000 (95% CI,13.22 to 31.82) for all populations,17.64 per 100 000 (95% CI,9.41 to 25.87)for men,and 27.94 par 100 000 (95% CI,17.58 to 38.30)for women.Age standardization to China's 2010 population yielded an estimated population of 304 954 cases with PBT.Our prevalence estimates provide a conservative basis on which to plan health care services and to develop programmatic strategies for surviving.In the future,it would be helpful to have long-term observed survival rates that would make the assumptions and the resulting imprecision in the current estimates unnecessary。

Abstract：Background Central neurocytoma accounts for 0.1% of primary brain tumor that often occurs in young adults.Surgery is the main treatment for central neurocytoma and the rate of 5-year survival reaches up to over 90%.This study aimed to assess the effect of transcortical frontal approach to surgical resection of central neurocytoma on emotion and cognitive function 5 years after surgery.Methods Telephone following-up visits were used in this study.By means of neuropsychological testing,assayed emotion,memory and abstract thinking ability of 18 patients undergoing central neurocytoma resection by transcortical frontal approach for 5 years or more,with another 21 normal cases as control group were enrolled.The data were analyzed statistically by paired t test with SPSS11.5.Results Patients whose central neurocytoma was removed by transcortical frontal approach were not affected on calculating ability 5 years after operation while ability of memory declined sharply (P=0.000),the older,the more sharply (P=0.036).Ability of abstract thinking was significantly reduced (P=0.000),the older,the more significantly as well (P=0.012);additionally,anxiety and depression occurred in patients rather more than those of control group (P=0.000),especially cognitive impairment.Conclusions Transcortical frontal approach for surgical resection of central neurocytoma has certain long-term influence on patients' life quality,vulnerable to anxiety,depression and cognitive impairment,the severity of which was correlated to age.Therefore,improving surgical approach will be of value for better long-term life quality of patients。

Abstract：Background Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy.Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies,it is not clear whether cancer stem cells are involved in invasiveness.This study aimed to assess invasive ability of glioma stem cells (GSCs) derived from C6 glioma cell line and the distribution patterns of GSCs in Sprague-Dawley (SD) rat brain tumor.Methods Serum-free medium culture and magnetic isolation were used to gain purely CD133+ GSCs.The invasive stem cell markers and luxol fast blue staining for white matter tracts were performed to show the distribution patterns of GSCs in brain tumor of rats and the relationship among GSCs,vessels,and white matter tracts.The results of matrigel invasion assay were estimated using the Student's t test and the analysis of Western blotting was performed using the one-way analysis of variance (ANOVA) test.Results CD133+GSCs(number:85.3±4.1)were significantly more invasive in vitro than matched CD133- cells(number:25.9±3.1) (t=14.5,P ＜0.005).GSCs invaded into the brain diffusely and located in perivascular niche of tumor-brain interface or resided within perivascular niche next to white fiber tracts.The polarity of glioma cells containing GSCs was parallel to the white matter tracts.Conclusions Our data suggest that CD133+ GSCs exhibit more aggressive invasion in vitro and GSCs in vivo probably disseminate along the long axis of blood vessels and transit through the white matter tracts.The therapies targeting GSCs invasion combined with traditional glioblastoma multiforme therapeutic paradigms might be a new approach for avoiding malignant glioma recurrence。

Abstract：Background Amyloid β1-42 (Aβ42) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models.But the phase Ⅱ trial of Aβ42 peptide vaccine was halted because of T cell-mediated meningoencephalitis.In this study,a DNA vaccine,p(Aβ3-10)10-CpG,was constructed to test whether it would induce predominant TH2 immune response upon immunization of BALB/c mice.Methods BALB/c mice were vaccinated intramuscularly with p(Aβ3-10)10-CpG plasmids.Aβ42 peptide,pcDNA3.1(+)empty vector and PBS were injected to the control groups.Expression of interesting gene in injected muscle was identified by immunohistochemistry.Anti-Al3 antibody titers,isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).Results P(Aβ3-10)10-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry.The p(Aβ3-10)10-CpG vaccine induced high titers of anti-Aβ antibodies in BALB/c mice.And isotype of the antibodies was mainly IgG1,the IgG1/IgG2a ratio for the p(Aβ3-10)10-CpG group was approximately 5 times greater than that for the Aβ42 peptide group.Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ3-10)10-CpG exhibited high interleukin-4 response and low interleukin-Y (IFN-Y) response.Conclusions Immunization with p(Aβ3-10)10-CpG vaccine primarily induces a TH2 type of response,thus reduces the probability of inflammation.This p(Aβ3-10)10-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine。

Abstract：Background Human amniotic epithelial cells (HAECs),which have characteristics of both embryonic and pluripotent stem cells,are therefore a candidate in cell therapy without creating legal or ethical problems.In the present study,we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer's disease (AD) coexpressing presenilin-1 (PS1) and mutant Sweden amyloid precursor protein (APPswe)genes.Methods The offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene.The doubly transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly divided into two groups respectively:the transplantation group treated with HAECs and the control group with phosphate buffered saline.Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice.Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively.Immunofluorescence cytochemistry was used to track the survival of HAECs.Immunohistochemistry was used to determine the expression of octamer-binding protein 4 (Oct-4) and Nanog in the HAECs.High performance liquid chromatography was used to measure acetylcholine in hippocampus.The density of cholinergic neurons in basal forebrain and nerve fibers in hippocampus was measured using acetylcholinesterase staining.Results Amyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months,but not in WT mice.The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection.The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell.Compared with the control group,transplantation of HAECs can not only significantly improve the spatial memory of the TG mice,but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites.Conclusions These results demonstrate that intracerebroventricular transplantation of HAECs can improve the spatial memory of the double TG mice.The higher content of acetylcholine in hippocampus released by more survived cholinergic neurites is one of the causes of this improvement。

Abstract：Background Although flunarizine has been widely used for migraine prophylaxis with clear success,the mechanisms of its actions in migraine prophylaxis are not completely understood.The aim of this study was to investigate the effects of flunarizine on tetrodotoxin-resistant Na+ channels and high-voltage activated Ca2+ channels of acutely isolated mouse trigeminal ganglion neurons.Methods Sodium currents and calcium currents in trigeminal ganglion neurons were monitored using whole-cell patch-clamp recordings.Paired Student's t test was used as appropriate to evaluate the statistical significance of differences between two group means.Results Both tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were blocked by flunarizine in a concentration-dependent manner with the concentration producing half-maximal current block values of 2.89 μmol/L and 2.73 μmol/L,respectively.The steady-state inactivation curves of tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were shifted towards more hyperpolarizing potentials after exposure to flunarizine.Furthermore,the actions of flunarizine in blocking tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were use-dependent,with effects enhanced at higher rates of channel activation.Conclusion Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks。

Abstract：Background In early April 2009,cases of human infection with 2009 pandemic influenza A (H1N 1) virus were identified in Mexico.The virus then spread rapidly to other regions of the world.From October 2009,sporadic imported cases of novel influenza A (H1N1) were continuously confirmed in Suzhou.The aim of the study was to review the chest CT findings in 63 patients with laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection.Methods Chest CT examinations were collected from 63 S-OIV infected patients during their hospital stay.Three experienced radiologists inspected images to qualitatively and quantitatively characterize S-OIV induced image changes.CT scores of lesion severity were calculated based on the percentage of affected area to determine severity of infectious lesions.Patients were divided into two groups based on the leukocyte counts.Lesion patterns,local distributions,and quantitative measures were investigated and compared between the two groups.Results Various degrees of bilateral multifocal lesions of ground-glass opacities were found with or without consolidations on the chest CT images.The lesions were both bronchocentric and centrilobular.Patients with elevated leukocyte counts had more extensive lesions,in terms of severity and affected area,than the patients with normal leukocyte counts.The lesion severity scores of patients in the elevated leukocyte group were significantly higher than those of the normal leukocyte group in terms of the entire lung area (P ＜0.01),and upper (P ＜0.05) and lower (P ＜0.01)lobes as well.There were changes in the CT characteristics seen at follow-up as demonstrated by lesions absorption (P＜0.01),especially in the upper lobe of the lung (P ＜0.01),but less so in the middle lobe/lingual and lower lobe of the lung (P＞0.05).Conclusions The most common CT findings in S-OIV infection patients were bilateral multifocal distributed ground-glass opacities and consolidations.The lesions were located dominantly at bronchocentric and centrilobular areas.Lung lesions were more obviously absorbed in upper lobes between two examinations.The observations and analysis from this study provide information that may be useful in image understanding and patient management for future pandemic influenza。

Abstract：Background Radiofrequency catheter ablation (RFCA) necessarily produces an area of myocardial necrosis.However,the difference of the extent of myocardial injury between circumferential pulmonary vein isolation (CPVI) and complex fractionated atrial electrograms (CFAE) ablation in patients with atrial fibrillation (AF) has not been investigated before.Methods Twenty-nine consecutive male patients (n=29) with either paroxysmal or persistent AF were selected for CPVI or CFAE ablation.The CPVI or CFAE ablation was performed with a three-dimensional electroanatomical mapping system (CARTO).Serum cardiac biomarkers,for example,cardiac troponin T (cTnT),aspartate transaminase (AST),lactate dehydrogenase (LDH),creatine kinase (CK),and creatine kinase myocardial bound (CKMB) were determined by the Elecsys STATE immunoassay.Cardiac structure and function were measured with echocardiography.Results Echocardiography showed that there was no significant difference of atrioventricular structure or function parameters between the CPVI group and the CFAE ablation group.Serum cTnT showed a significant increase in the CFAE ablation group over the CPVI group at 12 and 24 hours after the procedure (P＜0.05,respectively),and then it was reduced to a normal level after 48 hours.Serum AST showed a significant increase in the CFAE ablation group over the CPVI group at post-procedure,4 and 12 hours after the procedure (P ＜0.05,respectively),and then it reached to a normal level after 24 hours.There was no significant difference in LDH,CK,or CKMB levels between the CFAE ablation group and the CPVI group at any time point (P＞0.05).Conclusions cTnT and AST other than LDH,total CK or CKMB activity significantly increased more in the CFAE ablation group than the CPVI group.However,the difference of the serum levels of cTnT,AST between two groups was temporary。

Abstract：Objective To review the leading roles of glioma stem cells (GSCs) and their sophisticated interactions with other cells in the tissue remodeling process of gliomagenesis.Data sources Published articles about assessing GSCs in tumor initiation,progression,and multiple interactions with other cells in the special microenvironment were selected using PubMed.The search terms were "glioma stem cells","tumorigenesis",and "microenvironment".Study selection Articles regarding the tissue remodeling of GSCs in gliomagenesis were selected.Results GSCs exhibit enhanced tumor-initiating ability,could reestablish tumor,and were resistant to radiotherapy and chemotherapy.Studying the role of GSCs in gliomagenesis helps to develop targeting therapy against GSCs,which seems to be a cure for gliomas.However,sophisticated interactions between GSCs and their local microenvironment during tumor remodeling,including integrating with partially differentiated tumor cells,GSCs niche,neural stem cells (NSCs),normal glia,tumor-infiltrating lymphocytes,may obscure the leading role of GSCs during gliomagenesis,and make single targeting therapy unsuccessful.Conclusions Understanding the biological behavious of GSCs and their regulatory mechanisms may directly impact current efforts for more directed therapeutics against the highly aggressive gliomas.For multiple possible sources to turning into GSCs,simply eradicating the existing GSCs is not enough to be a cure for gliomas,blocking the potentialsources of GSCs and ameliorating the local tumor inducing/promoting microenvironment should be a reasonable strategy。

Abstract：Background Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin,and to have a greatly increased risk of bleeding.The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.Methods Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA.The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium.Results Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment,with target international normalized ratio (INR) 2 to 3.Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d.They needed more than 1 month to stabilize their anticoagulation.Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d.Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d.No concomitant medicine to increase or decrease the INR value was recorded for them.Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles-CYP2C9*3/*3 and VKORC1-1639 A/A.Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses.Conclusions Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin.The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes,as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy。

Abstract：Background The acute abdomen remains a challenge for all obstetricians and physicians who take part in the care of women in pregnancy.To add substantially to our understanding of acute pancreatitis (AP) in pregnancy,in particular affirming the increased risks for mother and fetus associated with AP,we explored features of clinical manifestation and the strategy of management of this disease during pregnancy,and its effects on maternal and fetal outcomes.Methods A retrospective review of medical records of all pregnant patients diagnosed with AP admitted to the Department of Obstetrics and Gynecology,Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between 2005 and 2010 was performed.Information was collected from presentation,management,and outcome from medical records.Results There were 11 cases in 2010,accounting for 44% of 25 cases.Among these cases,mild AP (MAP) occurred in 15 cases (60%),while the rest cases were severe AP (SAP) (40%).The major etiology of AP in pregnancy was due to gallstone and cholecystitis.Clinical features together with elevation of the plasma concentrations of pancreatic enzymes were the cornerstones of diagnosis.Positive conservative treatment was taken in most of the cases (21 cases,84%) with a favorable outcome.Seven cases of critically ill patients were monitored in intensive care unit,and 4 patients underwent surgical interventions.As a result,all of 25 patients had better prognosis,no maternal death was observed.There were 8 preterm labors and 2 fetal losses,accounting for the perinatal mortality of 8%.Fetal malformation was not observed.Conclusions While a pregnant woman suffers acute abdominal pain,early diagnosis and severity assessment of AP are very important.Conservative comprehensive treatment with intensive care is recommended.Surgical intervention should be performed as late as possible。

Abstract：Background Congenital quadricuspid aortic valve is rarely seen during aortic valve replacement (AVR).The diagnosis and treatment of the disease were reported in 11 cases.Methods Eleven patients (nine men and two women,mean age 33.4 years) with quadricuspid aortic valve were retrospectively evaluated.Medical records,echocardiograms and surgical treatment were reviewed.Results In accordance with the Hurwitz and Roberts classification,the patients were classified as type A (n=2),type B (n=7),type F (n=1) and type G (n=1).Three patients were associated with other heart diseases,including infective endocarditis and mitral prolaps,left superior vena cava,aortic aneurysm.All had aortic regurgitation (AR) except two with aortic stenosis (AS),detected by color-flow Doppler echocardiography.The congenital quadricuspid aortic valve deformity in seven patients was diagnosed by echocardiography.All patients underwent successful aortic valve replacement.Conclusion Quadricuspid aortic valve is a rare cause of aortic insufficiency,while echocardiography plays an important role in diagnosing the disease.Aortic valve replacement is the major therapy for the disease。

Abstract：Primary angiitis of the central nervous system is a rare and difficult entity.Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis.The 50-year-old male had a fluctuating disease course for more than 3 years.He presented visual disorders,seizure,cognitive impairment,hypersomnia,unsteady gait,dysphasia,dysphagia,and incontinence.Magnetic resonance imaging showed multiple,supratentorial and infratentorial abnormal signals,while cerebrospinal fluid and cerebral angiography were normal.Magnetic resonance spectrum showed a decrease of N-acetyl-aspartate.Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis,cicatrization,demyelination and focal hemorrhages。

Abstract：Fisher-Bickerstaff syndrome (FBS) was recently proposed to help to diagnose the conditions that overlap Fisher syndrome and Bickerstaff's brainstem encephalitis,as well as the unclassified conditions that had ophthalmoplegia and ataxia with clear consciousness,flexor plantar response and preserved tendon reflexes.Recurrences are exceptional presented with recurrent drowsiness,unsteady gait,diplopia and reduced deep tendon reflexes,which met the diagnostic criteria for FBS.The interval was eight months.He was treated with intravenous immunoglobulins during each episode and got good recovery.To our knowledge,this is a relatively early report about recurrent FBS case that had central and peripheral involvement during each episode in China。

Abstract：Pancreaticoduodenal artery pseudoaneurysm is one kind of rare splanchnic artery aneurysm.Hemorrhage from the lesion could be life-threatening.We present a case which color Doppler ultrasound and computed tomography angiography (CTA) only showed pancreatic pseudocyst on the background of chronic pancreatitis at first,but contrast-enhanced ultrasound detected blood flow in the pseudocyst and a pancreaticoduodenal artery pseudoaneurysm was worked up several days after.Finally,the pancreaticoduodenal artery pseudoaneurysm was confirmed by digital subtracted angiography.It might suggest the potential advantage of contrast-enhanced ultrasound in evaluating this kind of disease in comparison of CTA。

Abstract：Splenic cysts are unusual in daily surgical practice and less than 1000 cases have been reported.Primary,true or epithelial splenic cysts,are even rarer.Usually,most of the cysts are asymptomatic until of significant size,at which time they are then detected incidentally on ultrasonography or CT scan.We report a case of a 25-year-old woman with giant epithelial splenic cyst with about 3000 mi of clear-yellow fluid was collected from the cyst.The splenectomy specimen measured 205 mm×192 mm×137 mm and weighed 4000 g。