2012年 · 第125卷第24期

Gliomas,particularly glioblastomas (GBMs),are the most common and highly aggressive primary brain tumors with poor prognosis.In the past decade,a great many advances have been made in the study on cellular and molecular basis of gliomas.Numerous publications have explored the cell of origin of gliomas,the molecular genetic and epigenetic aberration in gliomas,the molecular classification of GBM subtypes,the possible oncometabolites,the application of targeted therapy for malignant gliomas,etc.However,considering all these findings in recent years,it is clear that a picture of the changes in gliomas is more complex and that it should be characterized further to gain a comprehensive and in-depth understanding of gliomagenesis and for translational application of the new insights into clinical practice,especially in the following important aspects。

Abstract：Background Intraoperative magnetic resonance imaging (iMRI) dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI (＜1.0T).This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan Hospital,Shanghai,China.Methods From September 2010 through March 2012,373 consecutive patients underwent neurological surgery under guidance with 3T iMRI.A retrospective analysis was conducted regarding clinical efficiency.Results All surgery in the 373 patients was safe.The ratio of gross total resection for cerebral gliomas (n=161) was increased from 55.90％ to 87.58％.The ratio of benefit in extent of resection was 39.13％.One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively.Twenty of 161 patients (12.42％) suffered from early motor deficit after surgery.Late motor deficit was however observed in five of 158 patients (3.16％).Twenty-one of 161 patients (13.04％) had early speech deficit and late speech deficit was only observed in six of 158 patients (3.80％).The ratio of gross total resection for pituitary adenomas (n=49) was increased from 77.55％ to 85.71％.The ratio of benefit in extent of resection was 10.2％.There were no iMRI-related adverse events even for patients who underwent awake craniotomy.Conclusion The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation,resulting in an improvement in maximal safe brain surgery。

Abstract：Background Reliable early prediction response to therapy and time-to-progression (TTP) remain an important goal of high-grade gliomas (HGGs) research.Proton magnetic resonance spectroscopy (1H-MRS) has been applied with variable success in clinical application,and we hypothesize that 1H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy (RT) after surgery.Methods 1H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine (Lip/Cr) and myo-inositol/creatine (ml/Cr) were determined in the solid tumor.RT response was classified as follows:complete resolution (CR),partial response (PR),stable disease (SD),and progressive disease (PD) by comparison of pre-treatment and post-radiotherapy scans.TTP was defined at the time to radiographic progression by MacDonald criteria.Correlation was evaluated between the ratios of Lip/Cr,ml/Cr and treatment response,TTP.The chi-square test and Pearson correlation test were used for data analyses.Results Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age,sex,WHO histologic grade,extent of surgery,and Karnofsky score (KPS).The correlation between the ratios of lipid/Cr and TTP was significant (r=0.894,P=0.000),and between the ratios of ml/Cr and TTP was also significant (r=0.891,P=0.000).As predicted,RT response correlated significantly with TTP (r=0.59,P=0.002):median TTP was 49.9 days for patients with PD compared with 202.7 days for SD,208.0 days for PR,and 234.5 days for CR.Conclusion The ratios of Lip/Cr and ml/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery。

Abstract：Background Treatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy.In this study,we intended to investigate the effects of 2-propylpentanoic acid (VPA),a histone deacetylase inhibitor,on chemosensitivity and radiosensitivity in human glioma cell lines.Methods Human glioma cell lines,T98-G,and SF295,were treated with temozolomide (TMZ) or irradiation (IR),with or without VPA (1.0 mmol/L).Then,cytotoxicity and clonogenic survival assay was performed.Cell cycle stage,apoptosis,and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay.One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.Results Mild cytotoxicity of VPA was revealed in both cell lines,T98-G and SF295,with the 50％ inhibiting concentration (IC50) value of (3.85±0.58) mmol/L and (2.15±0.38) mmol/L,respectively; while the IC50 value of TMZ was (0.20±0.09) mmol/L for T98-G and (0.08±0.02) mmol/L for SF295.Moreover,if combined with VPA (1.0 mmol/L) for 96hours,the sensitivity of glioma cells to TMZ was significant increased (P ＜0.05).The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58.However,when VPA was combined with IR,the SF2 of T98-G and SF295 dropped to 0.39 (P=0.047) and 0.49 (P=-0.049),respectively.Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P ＜0.01).Conclusion VPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy,and thus could be a potential sensitizer of glioma treatment。

Abstract：Background The primary reasons for local recurrence and therapeutic failure in the treatment of malignant gliomas are the invasion and interactions of tumor cells with surrounding normal brain cells.However,these tumor cells are hard to be visualized directly in histopathological preparations,or in experimental glioma models.Therefore,we developed an experimental human dual-color in vivo glioma model,which made tracking solitary invasive glioma cells possible,for the purpose of visualizing the interactions between red fluorescence labeled human glioma cells and host brain cells.This may offer references for further studying the roles of tumor microenvironment during glioma tissue remodeling.Methods Transgenic female C57BL/6 mice expressing enhanced green fluorescent protein (EGFP) were crossed with male Balb/c nude mice.Then sib mating was allowed to occur continuously in order to establish an inbred nude mice strain with 50％ of their offspring that are EGFP positive.Human glioma cell lines U87-MG and SU3 were transfected with red fluorescent protein (RFP) gene,and a rat C6 glioma cell line was stained directly with CM-Dil,to establish three glioma cell lines emitting red fluorescence (SU3-RFP,U87-RFP,and C6-CM-Dil).Red fluorescence tumor cells were inoculated via intra-cerebral injection into caudate nucleus of the EGFP nude mice.Tumor-bearing mice were sacrificed when their clinical symptoms appeared,and the whole brain was harvested and snap frozen for further analysis.Confocal laser scanning microscopy was performed to monitor the mutual interactions between tumor cells and host brain cells.Results Almost all the essential tissues of the established EGFP athymic Balb/c nude mice,except hair and erythrocytes,fluoresced green under excitation using a blue light-emitting flashlight with a central peak of 470 nm,approximately 50％ of the offsprings were nu/nu EGFP+.SU3-RFP,U87-RFP,and C6-CM-Dil almost 100％ expressed red fluorescence under the fluorescence microscope.Under fluorescence microscopic view,RFP+ cells were observed growing wherever they arrived at,locating in the brain parenchyma,ventricles,and para-vascular region.The interactions between the transplanted tumor cells and host adjacent cells could be classified into three types:(1) interweaving; (2)mergence; and (3) fusion.Interweaving was observed in the early stage of tumor remodeling,in which both transplantable tumor cells and host cells were observed scattered in the tumor invading and spreading area without organic connections.Mergence was defined as mutual interactions between tumor cells and host stroma during tumorigenesis.Direct cell fusion between transplantable tumor cells and host cells could be observed occasionally.Conclusions This study showed that self-established EGFP athymic nude mice offered the possibility of visualizing tumorigenesis of human xenograft tumor,and the dual-color xenograft glioma model was of considerable utility in studying the process of tumor remodeling.Based on this platform,mutual interactions between glioma cells and host tissues could be observed directly to further elucidate the development of tumor microenvironment。

Abstract：Background Non-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however,the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined.The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy,low-intensity warfarin therapy,and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).Methods A total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups:standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group,low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group.All patients were evaluated by physicians at 1,3,6,9,12,15,18,21 and 24 months after randomization to obtain a patient questionnaire,physical examination and related laboratory tests.Results The annual event rates of ischemic stroke,transient ischemic attack (TIA) or systemic thromboembolism were 2.6％,3.1％ and 6.9％ in the standard-intensity warfarin,low-intensity warfarin and aspirin groups,respectively (P=0.027).Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P=0.018,P=0.044),and there was no significant difference between the two warfarin groups.Severe hemorrhagic events occurred in 15 patients,7 (2.6％) in the standard-intensity warfarin group,7 (2.4％) in the low-intensity warfarin group and 1 (0.4％)in the aspirin group.The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group,but the difference did not reach statistical significance (P=0.101).The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2％,7.6％ and 2.2％,respectively,in the 3 groups (P=0.001).Furthermore,there was no significant difference in all cause mortality among the three study groups.Conclusion In Chinese patients with NVAF,the warfarin therapy (INR 1.6-2.5) for the prevention of thromboembolic events was superior to aspirin。

Abstract：Background Despite considerable improvements in the care of patients with cardiovascular disease in various populations over the last few decades,there are still limited data about long-term treatment patterns among patients with various atherosclerotic vascular conditions in China,especially the use of statin therapy.Methods Between June 2007 and October 2009,16 860 patients aged 50-80 years with established history of atherosclerotic vascular disease (coronary heart disease (CHD),atherosclerotic cerebrovascular disease (CVD),or peripheral arterial disease (PAD)) from 51 hospitals in 14 cities of China were screened for a large randomized trial.Detailed information about current use of statins and various other treatments was recorded and analyzed by prior disease history,adjusting for various baseline characteristics.Results Among the 16 860 patients,the mean age was 63 years and 74％ were male.Overall,78％ of the patients had documented CHD,40％ had CVD,5％ had PAD and 21％ reported more than one condition.The median time from initial diagnosis of vascular disease to screening was 18 months.At screening,the proportions who took various treatments were 83％ for antiplatelet agents,49％ for beta-blockers,47％ for statins and 28％ for angiotensin-converting enzyme inhibitors.The proportion treated with statin was much higher in CHD than in CVD or PAD patients (61％ vs.10％ vs.22％ respectively) and decreased significantly with time from initial diagnosis.Simvastatin (mainly 20 mg) and atorvastatin (mainly 10 mg) each accounted for about 40％ of total statin use.Conclusions In urban China,there is still significant underuse of various proven secondary preventive therapies,with particularly low use of statins in patients with ischaemic stroke。

Abstract：Background The effects of anxiety and depression on the recurrence of persistent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA) are not clear.Whether CPVA can alleviate the anxiety and depression symptoms of persistent AF patients is unknown.Methods One hundred and sixty-four patients with persistent AF,of which 43 treated with CPVA (CPVA group) and 103 treated with anti-arrhythmics drugs (medicine group),were enrolled.The Zung Self-Rating Anxiety Scale (SAS),and Zung Self-Rating Depression Scale (SDS) were assessed before and 12 months after treatment in all patients.Results The scores of SAS (40.33±7.90 vs.49.76±9.52,P ＜0.01) and SDS (42.33±8.73 vs.48.17±8.77,P ＜0.01)decreased 12 months after CPVA.Over 12 months follow-up,AF relapsed in 17 patients in CPVA group.Compared with the data in the recurrent group (17 patients),the scores of SAS and SDS were significantly lower in the non-recurrent group (26 patients) at baseline.The results of multivariate Logistic regression analysis showed normal scores of SAS and SDS were the independent risk factors of AF recurrence after CPVA.Conclusions Anxiety and depression increase the recurrence risk of persistent AF after CPVA.CPVA can ameliorate the anxiety and depression symptoms in patients with persistent AF。

Abstract：Background The most appropriate surgical approach for patients with post-infarction left ventricular (LV) aneurysm remains undetermined.We compared the efficacy of the linear versus patch repair techniques,and investigated the mid-term changes of LV geometry and cardiac function,for repair of LV aneurysms.Methods We reviewed the records of 194 patients who had surgery for a post-infarction LV aneurysm between 1998 and 2010.Short-term and mid-term outcomes,including complications,cardiac function and mortality,were assessed.LV end-diastolic and systolic dimensions (LVEDD and LVESD),LV end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) and LV ejection fraction (LVEF) were measured on pre-operative and follow-up echocardiography.Results Overall in-hospital mortality was 4.12％,and major morbidity showed no significant differences between the two groups.Multivariate analysis identified preoperative left ventricular end diastolic pressure ＞20 mmHg,low cardiac output and aortic clamping time ＞2 hours as risk factors for early mortality.Follow-up revealed that LVEF improved from 37％ pre-operation to 45％ 12 months post-operation in the patch group (P=0.008),and from 44％ pre-operation to 40％ 12 months postoperation in the linear group (P=0.032).In contrast,the LVEDVI and LVESVI in the linear group were significantly reduced immediately after the operation,and increased again at follow-up.However,in the patch group,the LVEDVI and LVESVI were significantly reduced at follow-up.And there were significant differences in the correct value changes of LVEF and left ventricular remodeling between linear repair and patch groups.Conclusions Persistent reduction of LV dimensions after the patch repair procedure seems to be a procedure-related problem.The choice of the technique should be tailored on an individual basis and surgeon's preference.The patch remodeling technique results in a better LVEF improvement,further significant reductions in LV dimensions and volumes than does the linear repair technique.The results suggest that LV patch remodeling is a better surgical choice for patients with post-infarction LV aneurysm。

Abstract：Background Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes.How to stabilize vulnerable plaques is still a challenge to medical science.Alprostadil is a biologically active substance with strong activity on vessel.Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice.Methods Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age.At week 17,they were divided randomly into groups for treatment with a high dose (3.6 μg · kg-1 · d-1) or low dose (1.8 μg · kg-1 · d-1) of an ALMP,or 0.2 ml/d normal saline (control group).The drug was administered using a micro-capsule pump.Twenty weeks after drug administration,pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed,and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence.The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA,and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR.Thrombospindin-1 (TSP-1) expression was detected using Western blotting.Results Compared with the control group,ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P ＜0.01),significantly lowered the contents of the lipid core (P ＜0.01),significantly reduced the number of ruptured fibrous caps (P ＜0.05),and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P ＜0.05).ALMP treatment significantly reduced the expression of MOMA-2,superoxide anion,MMP-9,ICAM-1 and CD40 in the plaques (P ＜0.01),decreased plasma ICAM-1 expression (P ＜0.01),and increased the expression of TSP-1.Conclusions Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation。

Abstract：Background Dicycloplatin is a relatively safe third generation platinum-complex anti-cancer drug.The present study focused on the effects of dicycloplatin on in vitro proliferation and apoptosis of human aortic smooth muscle cells (HASMC) and human aortic endothelial cells (HAEC).Methods Proliferation of HASMC and HAEC,DNA content,and cellular levels of proliferation-and apoptosis-related proteins were assessed using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay,flow cytometry and Western blotting assays,respectively.Results Dicycloplatin at 10 ng/ml significantly inhibited HASMC proliferation,however,10 μg/ml were required to significantly inhibit HAEC proliferation.Cell cycle analysis showed that dicycloplatin was a non-specific inhibitor of the cell cycle.Although dicycloplatin significantly decreased proliferating cell nuclear antigen (PCNA) expression in HASMC at all concentrations tested,it did not significantly affect PCNA expression in HAEC; Bax and p53 protein expression was upregulated in dicycloplatin groups.Conclusions Dicycloplatin at nanogram concentrations significantly inhibits HASMC proliferation,although the effect is relatively weaker than that of sirolimus.In contrast,the effect of dicycloplatin on inhibition of HAEC proliferation is much less pronounced than that on HASMC The latter characteristics point to the potential for use of dicycloplatin in drug-eluting stents。

Abstract：Background Recent studies have suggested that cancer stem cells are one of the major causes for tumor recurrence due to their resistance to radiotherapy and chemotherapy.Although the highly invasive nature of glioblastoma (GBM)cells is also implicated in the failure of current therapies,it is not clear how glioma stem cells (GSCs) are involved in invasiveness.Rac1 activity is necessary for inducing reorganization of actin cytoskeleton and cell movement.In this study,we aimed to investigate the distribution characteristics of CD133+ cells and Rac1+ cells in GBM as well as Rac1 activity in CD133+ GBM cells,and analyze the migration and invasion potential of these cells.Methods A series of 21 patients with GBM were admitted consecutively and received tumor resection in Tianjin Medical University General Hospital during the first half of the year 2011.Tissue specimens were collected both from the peripheral and the central parts for each tumor under magnetic resonance imaging (MRI) navigation guidance.Immunohistochemical staining was used to detect the CD133+ cells and Rac1+ cells distribution in GBM specimens.Double-labeling immunofluorescence was further used to analyze CD133 and Rac1 co-expression and the relationship between CD133+ cells distribution and Rac1 expression.Serum-free medium culture and magnetic sorting were used to isolate CD133+ cells from U87 cell line.Rac1 activation assay was conducted to assess the activation of Rac1 in CD133+ and CD133-U87 cells.The migration and invasive ability of CD133+ and CD133-U87 cells were determined by cell migration and invasion assays in vitro.Student's t-test and one-way analysis of variance (ANOVA) test were used to determine statistical significance in this study.Results In the central parts of GBMs,CD133+ cells were found to cluster around necrosis and occasionally cluster around the vessels under the microscope by immunohistological staining.In the peripheral parts of the tumors,CD133+ cells were lined up along the basement membrane of the vessels and myelinated nerve fibers.Rac1 expression was high and diffused in the central parts of the GBMs,and the Rac1+ cells were distributed basically in accordance with CD133+ cells both in the central and peripheral parts of GBMs.In double-labeling immunofluorescence,Rac1 was expressed in (83.14±4.23)％ of CD133+ cells,and CD133 and Rac1 co-expressed cells were located around the vessels in GBMs.Significantly higher amounts of Rac1-GTP were expressed in the CD133+ cells (0.378+0.007),compared to CD133-cells (0.195±0.004) (t=27.81; P ＜0.05).CD133+ cells had stronger ability to migrate (74.34±2.40 vs.38.72±2.60,t=42.71,P ＜0.005) and invade (52.00±2.28 vs.31.26±1.82,t=30.76,P ＜0.005),compared to their counterpart CD133-cells in transwell cell migration/invasion assay.Conclusions These data suggest that CD133+ GBM cells highly express Rac1 and have greater potential to migrate and invade through activated Rac1-GTP.The accordance of distribution between Rac1+ cells and CD133+ cells in GBMs implies that Rac1 might be an inhibited target to prevent invasion and migration and to avoid malignant glioma recurrence。

Abstract：Objective To review recent studies concerning the origins of skin-derived precursors (SKPs),their differentiation characteristics,and their potential application in neural regenerative medicine.Data sources Data were retrieved from studies reported in PubMed published between April,1974 and June,2012.The search terms used were "skin-derived precursors","stem cells",and "neural diseases".Study selection Articles were included in the review if they were relevant to SKPs as stem cells,as well as their applications in neural regenerative medicine,such as in the treatment of spinal cord injury,Parkinson's disease,spinal muscular atrophy and Shah-Waardenburg syndrome.Results SKPs are a novel population of neural crest-derived precursors that arise during embryogenesis and persist into adulthood.They can generate both neural cells and mesodermal lineage cells (including smooth muscle cells and adipocytes).Compared with other stem cells,SKPs are abundant in adult skin,can differentiate easily into neural cells,and are not associated with any ethical controversies.Conclusion SKPs may provide an alternative source of stem cells to embryonic stem cells for transplantation therapy for neurological diseases。

Abstract：Objective To review the history,development,and reality of neuronavigation surgery in China and to discuss the future of neuronavigation surgery.Data sources PubMed,the China Knowledge Resource Integrated Database,and the VIP Database for Chinese Technical Periodicals were searched for papers published from 1995 to the present with the key words "neuronavigation,""functional navigation," "image-guided," and "stereotaxy." Articles were reviewed for additional citations,and some information was gathered from Web searches.Study selection Articles related to neuronavigation surgery in China were selected,with special attention to application to brain tumors.Results Since the introduction of neurosurgical navigation to China in 1997,this core technique in minimally invasive neurosurgery has seen rapid development.This development has ranged from brain structural localization to functional brain mapping,from static digital models of the brain to dynamic brain-shift compensation models,and from preoperative image-guided surgery to intraoperative real-time image-guided surgery,and from application of imported equipment and technology to use of equipment and technology that possess Chinese independent intellectual property rights.Conclusions The development and application of neuronavigation techniques have made neurological surgeries in China more safe,precise and effective,and less invasive,and promoted the quality of Chinese neurosurgical practice to the rank of the most advance and excellence in the world。

Abstract：Objective This literature review aims to summarize the methods of isolation,expansion,differentiation and preservation of human umbilical cord mesenchymal stem cells (hUCMSCs),for comprehensive understanding and practical use in preclinical research and clinical trials.Data sources All the literature reviewed was published over the last 10 years and is listed in PubMed and Chinese National Knowledge Infrastructure (CNKI).Studies were retrieved using the key word "human umbilical cord mesenchymal stem cells".Results Explants culture and enzymatic digestion are two methods to isolate hUCMSCs from WJ and there are modifications to improve these methods.Culture conditions may affect the expansion and differentiating orientations of hUCMSCs.In addition,hUCMSCs can maintain their multi-potential effects after being properly frozen and thawed.Conclusion Considering their multi-potential,convenient and non-invasive accessibility,low immunogenicity and the reported therapeutic effects in several different preclinical animal models,hUCMSCs have immense scope in regeneration medicine as a substitute for MSCs derived from bone marrow or umbilical cord blood。

Abstract：Glioma is the most malignant tumor in the brain,the origin of glioma is still unknown.Recently some papers indicated that glioma may be developed from cerebral cavernous malformation (CCM).We describe a man with a right temporal lobe CCM,after gamma-knife radiotherapy,the patient developed a low-grade astrocytoma in the area of the preexistent CCM.This case,together with other reports,may indicated an oncogenetic properties of CCM,and we proposed that CCM may be a pre-glioma lesion。

Abstract：Cystic tumour of the atrioventricular node is a rare primary cardiac tumour that can cause complete heart block and sudden death.Here,we describe a male case aged 42 years who suddenly died without a medical and family history of cardiac illnesses.After detailed macroscopic and microscopic examinations,a cystic mass was found in the atrioventricular nodal region.The small lesion was less than 1 cm in diameter,and consisted of small and large cystic spaces and tubular structures lined by flat,cuboidal or squamous epithelium.Immunohistochemical staining revealed the tumour epithelium positive for epithelial membrane antigen,carcinoembryonic antigen,antigen epitopes AE1/AE3,cytokeratins CK5/6 and CK7,but negative for calretinin,HBME-1,Wilms' tumor 1,factor Ⅷ,chromogranin,synaptophysin or smooth muscle actin,suggesting an endodermal rather than mesothelial origin。

Abstract：Twin pregnancy with mosaic partial hydatidiform mole (PHM) and survival of two healthy fetuses following in vitro fertilization and embryos transfer (IVF-ET) is a rare situation and is considered a challenge for management.A 32-year-old Chinese woman conceived twin pregnancy following IVF-ET.At 22 weeks' gestation,an additional intrauterine echogenic mass with features of PHM were shown by successive ultrasound examinations.At 35 weeks'gestation,two live male infants and two placentas were delivered by caesarean section (CS).Histologic examination of the abnormal placenta confirmed mosaic PHM.Genetic study showed the abnormal placental mosaicism (expressed in molar-69XXY and normal vili-46XY),co-existing with a hypospadia new-born (46XY) in one amniotic sac.However,the other one was normal.Serial serum β-hCG levels showed a declining trend and serum 3-human chorionic gonadotropin (hCG) were undetectable at 6 months after delivery.The case demonstrated that it is possible to prolonged gestation by PHM under close surveillance during the entire pregnancy。

The malignant glioma is characterized by intrinsic aggressiveness and carries a dismal prognosis.The current standard treatment regimen for patients with malignant gliomas,specifically glioblastoma,is a combined therapy comprised of surgical resection followed by adjunctive radiation and chemotherapy.1 Yet,even with this new multimodality treatment,glioblastoma (GBM) recurs after a median time of 7 months following diagnosis,requiring a second-line treatment.But the clinical decisions are always difficult.Decisions regarding disease management are complicated by the fact that any change in the patient's radiological image suggesting disease progression may be due to radiation-induced injury。

Phacoemulsification with intraocular lens (IOL)implantation has become the most widely accepted and effective surgery for cataract patients.Although progress in this technique has greatly reduced surgery-related complications,visual acuity can be substantially compromised in certain circumstances,postoperatively.Cystoid macular edema (CME) is one of the most common complications and needs special attention.1

Gliomatosis cerebri (GC) is a diffuse glial tumor that infiltrates the brain extensively.The optimal therapeutic strategy for this tumor has not yet been established.Radiotherapy,temozolomide and other chemotherapeutic modalities have been used to treat GC.1,2 Despite aggressive and often multimodal therapeutic intervention,survival rates for adult and pediatric patients with GC are extremely poor.3 Here we report two cases of GC in which we initially explored a new therapeutic strategy for this disease。

Use of an apico-aortic conduit (AAC) serves as an alternative method to treat severe aortic stenosis in elder patients,especially in those with a heavily calcified ascending aorta or prior cardiac surgery.The results of long-term follow-up of AAC are very rare.We reported a case about a successful replacement of late degenerated prosthetic valve following AAC procedure,assisted with extra corporeal membrane oxygenation (ECMO)。

Aggressive fibromatosis is a rare disease.The pathological feature of the disease is that the tumor cells appear as benign in morphology,but aggressive in biological behavior.So the tumor infiltrates adjacent structures such as bone,vessels and nerves as well as having a high recurrence rate after surgical resection,but lacks the capacity for forming distant metastases.1,2 We here report a patient who underwent a series of imaging examinations and surgery。

A49-year-old woman with a history of rheumatic heart disease was admitted to the hospital because of worsening dyspnea and orthopnea with cyanosis of the four extremities.She underwent prosthetic mitral valve replacement 15 years ago for mitral stenosis.Due to prosthetic valve dysfunction and severe aortic regurgitation,she received both mechanical aortic and mitral valve replacements 2 years later。

Hydatid disease is a parasitic infestation by a tapeworm of the genus echinococcus.Spinal hydatidosis occurs in 1％ of all cases with hydatidosis and is most commonly located in the dorsal spine.1 It is a rare cause of neurological signs and symptoms.Spinal hydatid disease should be considered in the differential diagnosis of spinal cord compression syndrome in endemic areas.There are no characteristic signs or symptoms.Misdiagnosis is easily to be made preoperatively.Most diagnosis are made intraoperatively,which increases the risk of future recurrences.Here we reported a patient with slowly progressive weakness of lower limbs and aconuresis for 2 months due to L5-S1 spinal intradural hydatidosis compressing the cauda equine and the origin of the left L5-S 1 nerve root。

Scientific journals are more likely to publish those articles which will be highly cited after their publication.To improve the quality and the impact of the Chinese Medical Journal (CMJ),the distribution of highly cited articles published in CMJ in 2010 was analyzed and reported in this article。

To the editor:The endometrial lesion and uterus prolapsed of young woman presents a distinct feature in uterus prolapsed of systemic lupus erythematosus (SLE) patients,but it is receiving little consideration.To our knowledge,there are few reported cases of women with endometrial lesion and SLE.We here reported a case of endometrial complex hyperplasia and uterus prolapsed pelvic organ prolapse quantification system (POP-Q) stage Ⅲ of a 24-year-old woman with SLE。

To the editor:The recent article by Bao et al1 was highly interesting and thought provoking.Interestingly,recent data suggested that nifedipine may play a major role in oncology to overcome multi-drug resistance.For instance,nifedipine when administered to melanomas augments the anti-neoplastic effects of chemotherapeutic agents such as cisplatin.2 This synergistic inhibition of melanomas markedly decreases tumor size as well as metastasis.Similarly,nifedipine in conjunction with Ca(2+) enhances the chemo sensitivity of colon carcinomas to therapeutic agents such as 5-fluorouracil.3 It does this by activating G protein coupled calcium sensing receptors and thereby results in attenuated survivin expression.At the same time it inhibits the expression of thymidylate synthase.Similarly,nifedipine may be of clinical benefit in patients with colon cancer and underlying mismatch repair gene defects.This has been confirmed by Yang and Friedlander4 in a recent case report。

To the editor:There are reports on over expression of epidermal growth factor receptor (EGFR),vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in esophageal carcinomas (EC).1-3 We conducted a combined analysis on their expression in EC based on immunohistochemical and multiple regression analysis. A total of 114 cases of esophageal cancer confirmed by biopsy were enrolled in our hospital from January 2006 to December 2006,including 75 males and 39 females,aged 39 to 76 years (median 59 years).Thirty-one specimens with well differentiated squamous cell carcinoma,66 with moderately differentiated squamous cell carcinoma,13 with poorly differentiated squamous cell carcinoma and 4 specimens with adenocarcinoma were obtained。