清开灵和双黄连口服液体内抗禽流感病毒作用

目的 评价清开灵和双黄连口服液体内抗禽流感病毒药效,探讨其对感染流感病毒小鼠免疫功能的影响。方法 建立H9N2亚型禽流感病毒鼠肺适应株人工感染BALB/c小鼠模型,以肺指数抑制率、生命保护率和肺病毒滴度为主要评价指标,研究清开灵和双黄连口服液对感染H9N2亚型禽流感病毒小鼠的防治效果;以脾指数、胸腺指数和T细胞亚群比率（CD4⁺/CD8⁺）为主要评价指标,探讨清开灵和双黄连口服液对感染流感病毒小鼠免疫功能的影响。结果 清开灵和双黄连口服液均能显著抑制H9N2亚型禽流感病毒引起的小鼠肺炎实变,攻毒后第4天小鼠肺指数抑制率分别为34.1%、26.3%。清开灵和双黄连口服液对感染小鼠有显著的生命保护作用,存活率分别为70.0%、60.0%,显著高于病毒对照组的存活率（30.0%）,鼠肺病毒滴度显著低于病毒组（P＜0.01）。清开灵和双黄连口服液对感染病毒后小鼠脾脏和胸腺萎缩具有显著的抑制作用,并能提升感染小鼠脾脏中CD4⁺/CD8⁺值。结论 清开灵和双黄连口服液具有显著的抗禽流感病毒作用,对病毒复制的抑制及对病毒感染导致的小鼠免疫功能下降的调节作用是其发挥抗病毒功效的重要机制。     

Bedside chest radiography of novel influenza A （H7N9） virus infections and follow-up findings after short-time treatment

Background Influenza A （H7Ng） virus infections were first observed in China in March 2013.This type virus can cause severe illness and deaths,the situation raises many urgent questions and global public health concerns.Our purpose was to investigate bedside chest radiography findings for patients with novel influenza A （H7Ng） virus infections and the followup appearances after short-time treatment.Methods Eight hospitalized patients infected with the novel influenza A （H7Ng） virus were included in our study.All of the patients underwent bedside chest radiography after admission,and all had follow-up bedside chest radiography during their first ten days,using AXIOM Aristos MX and/or AMX-Ⅳ portable X-ray units.The exposure dose was generally 90 kV and 5 mAs,and was slightly adjusted according to the weight of the patients.The initial radiography data were evaluated for radiological patterns （ground glass opacity,consolidation,and reticulation）,distribution type （focal,multifocal,and diffuse）,lung zones involved,and appearance at follow-up while the patients underwent therapy.Results All patients presented with bilateral multiple lung involvement.Two patients had bilateral diffuse lesions,three patients had unilateral diffuse lesions of the right lobe with multifocal lesions of the left lobe,and the remaining three had bilateral multifocal lung lesions.The lesions were present throughout bilateral lung zones in three patients,the whole right lung zone in three patients with additional involvement in the left middle and/or lower lung zone（s）,both lower and middle lung zones in one patient,and the right middle and lower in combination with the left lower lung zones in one patient.The most common abnormal radiographic patterns were ground glass opacity （8/8）,and consolidation （8/8）.In three cases examined by CT we also found the pattern of reticulation in combination with CT images.Four patients had bilateral and four had unilateral pleural effusion.After a short period of treatment the pneumonia in one patient had significantly improved and three cases demonstrated disease progression.In four cases the severity of the pneumonia fluctuated.Conclusions In patients with influenza A （H7N9） virus infection,the distribution of the lung lesions are extensive,and the disease usually involves both lung zones.The most common imaging findings are a mixture of ground glass opacity and consolidation.Pleural effusion is common.Most cases have a poor short-time treatment response,and seem to have either rapid progressive radiographic deterioration or fluctuating radiographic changes.Chest radiography is helpful for evaluating patients with severe clinical symptoms and for follow-up evaluation.     

Human infection with a novel avian-origin influenza A （H7N9） virus： serial chest radiographic and CT findings

Background Rapidly progressive pneumonia infection with H7N9 virus is a novel disease,and limited information is available concerning serial chest radiographic and computed tomography （CT） findings.The aim of this study was to evaluate the changes in serial radiologic findings in patients with H7N9 pneumonia.Methods The two institutional ethics review boards approved this retrospective study.This study included 10 patients with H7N9 pneumonia.All patients underwent chest radiologic examinations at different time points.Serial radiologic images were systematically analyzed.Results All patients showed abnormal results on initial chest radiography and CT.The initial radiographic abnormalities were unilateral （n=9） and bilateral （n=1）,including ground-glass opacities （GGOs） （n=5） and consolidation （n=5）.The initial CT findings consisted of unilateral （n=6） and bilateral （n=4）,including consolidation （n=10）,GGOs （n=10）,reticular opacities （n=2）,and pleural effusion （n=3）.Follow-up radiologic findings showed rapid development of consolidation or GGOs within two weeks after illness onset.Pneumomediastinum with secondary subcutaneous emphysema and pneumothorax were noted in two patients.Follow-up high resolution computed tomography （HRCT） after two weeks showed slow improvement in both size and opacity of the lesions.On HRCT after discharge,patients had substantial residual lesions such as irregular linear opacities,reticular opacities,parenchymal bands,traction bronchiectasis,and cystic lesions.Conclusions The most common radiologic findings at presentation are multifocal or diffuse areas of consolidation and GGOs in H7N9 pneumonia.HRCT in sequence can show more changes in rapid progression of disease and a slow decrease of both size and opacity of the lesions plays an important role in the evaluation of H7N9 pneumonia.     

禽流感H5N1亚型病毒对五个不同品系小鼠致病性的比较

目的 比较了不同遗传背景小鼠对禽流感H5N1亚型病毒的致病敏感性,为H5N1禽流感模型制作和机理研究提供依据.方法 近交系BALB/c、C57BL/6和封闭群ICR、NIH Swiss和KM Swiss共五个不同品系小鼠.每个品系实验动物30只,分接毒组20只,空白对照组10只,每组雌雄各半.病毒株为A/Goose/Guangdong/NH/2003(H5N1),经测定TCID50为10-4.875/mL.接毒组通过鼻腔接种0.1 mL病毒液,对照组接种正常鸡胚尿囊液.小鼠接毒后连续观察14 d,观察记录临床症状、体温、体重变化,对在实验期间死亡和实验14 d结束后仍然存活的小鼠均进行组织器官病理取材,进行RT-PCR病毒分离检测、HE染色及H5N1抗原特异性免疫组化染色.结果 ①临床症状:H5N1禽流感病毒能感染五个品系的小鼠,引起呼吸急促等症状和一过性体重、体温下降.②死亡情况:小鼠在接毒后第1天即出现死亡,死亡的高峰期集中在接毒后第3～6天.五个品系小鼠死亡率存在差异,BALB/c为70%,ICR为50%,NIH Swiss为40%,C57BL/6为25%,KM Swiss为10%;③病毒分离:各组接毒小鼠在死亡后均进行了病毒分离,死亡小鼠的肺脏均分离到病毒,其他脏器未分离到病毒.④病理变化:实验期间五个品系死亡小鼠肺脏病理改变相近.大体观:死亡小鼠肺部淤血,呈暗红色,体积增大,局部肺组织实变.镜下观:死亡小鼠的共同病理改变为间质性肺炎,具体表现为肺泡腔及间质出血、炎性细胞浸润;间质增生,肺泡隔增宽;肺泡腔中见纤维素性渗出,透明膜形成.⑤免疫组化结果:在死亡小鼠的气管上皮细胞和肺巨噬细胞可观察到H5N1禽流感病毒阳性表达.结论 小鼠作为H5N1禽流感病毒模型具有普适性,不同品系小鼠感染鹅源H5N1禽流感病毒的临床症状、病程和病理变化与人禽流感病例相似.不同品系小鼠的死亡比例有明显差别,可以根据不同的实验目的,选择不同品系的小鼠制作H5N1禽流感动物模型.不同品系的遗传特性对禽流感易感性产生明显的影响,遗传背景可能与H5N1禽流感病毒感染应答机理存在联系:BALB/c和C57BL/6均为近交系,其中BALB/c小鼠的品系特征之一表现为干扰素产量低,接种H5N1病毒后表现为高死亡率(70%),而C57BL/6小鼠的干扰素产量高,接种H5N1病毒后表现为低死亡率(25%),提示不同遗传背景小鼠的干扰素水平与H5N1感染致死具相关性.为进一步研究H5N1禽流感病毒易感性相关基因以及其与宿主免疫反应的关系提供了一个研究基础.     

人H7N9禽流感病毒与H1N1流感病毒感染小鼠病理学损伤的比较

目的 比较分析H7N9病毒与H1N1病毒感染小鼠病理学损伤特点,初步探讨两种病毒感染致小鼠急性肺损伤的致病机制. 方法 H7N9病毒与H1N1病毒分别感染小鼠,观察不同病毒感染后小鼠生存率,并于不同时间点取心、肝、脾、肺、肾、脑、肠等组织,伊红-苏木素染色并进行组织病理学分析,免疫组化检测病毒抗原分布及中性粒细胞浸润.综合分析肺组织病理损伤与病毒复制、宿主免疫反应之间的关系. 结果 H7N9病毒感染小鼠肺及脾脏损伤较轻,存活率较高.H1N1 病毒感染的小鼠肺及脾脏损伤较重,感染后9 d全部死亡;两种病毒抗原主要分布于支气管上皮细胞、少量间质细胞和肺泡上皮细胞,病毒复制水平无明显差异.但H1N1病毒感染后肺及脾脏中均有大量中性粒细胞浸润,小鼠机体炎症反应明显强于H7N9病毒感染后小鼠炎症反应. 结论 H7N9病毒与H1N1病毒感染后小鼠病理学损伤特点及程度均不同,病毒复制是小鼠肺损伤的诱发因素但并非决定因素,宿主针对病毒感染产生的免疫反应程度与急性肺损伤密切相关.     

人H7N9禽流感病毒、高致病H5N1禽流感病毒及H1N1流感病毒感染小鼠特征分析

目的 对比分析人高致病H5N1禽流感病毒、H7N9禽流感病毒及H1N1流感病毒分别感染BALB/c小鼠后的机体反应特征。方法 分别以H7N9病毒、H5N1病毒和H1N1病毒滴鼻感染BALB/c小鼠,观察小鼠存活率、体征变化及感染后肺组织病理损伤差异,检测小鼠感染流感病毒后肺组织增殖细胞核抗原（PCNA）表达并观察小鼠感染后修复状况。结果 H7N9病毒、H5N1病毒和H1N1病毒均感染BALB/c小鼠,小鼠存活率依次为H7N9>H1N1>H5N1,肺组织病理损伤严重程度依次为H5N1 >H1N1 >H7N9,PCNA表达水平依次为H7N9 >H1N1 >H5N1。结论 H7N9病毒感染后宿主炎症反应较小,感染后小鼠肺组织自我修复能力较强;H5N1病毒感染BALB/c小鼠后的机体反应最为强烈,感染后恢复能力差,致死率高。     

新型H7N9病毒在同居小鼠中的传播途径

目的 进一步了解新型H7N9流感病毒的致病性、传播能力以及通过何种途径进行传播。方法 H7N9病毒感染小鼠后与同居小鼠合笼，研究同居小鼠的临床变化指征、病毒复制情况、病毒在组织中的分布以及病理变化。以同居小鼠分泌物接种其他小鼠，观察同居小鼠通过何种途径传播病毒。结果 H7N9病毒可以在肺组织、肠组织和脑组织中复制，并可以在同居小鼠中传播。H7N9病毒感染小鼠其咽、眼分泌物以及粪便均具有感染性，其中尤以咽拭子的传播风险最高。结论 H7N9病毒可以不通过适应就感染小鼠，并引起小鼠间传播。被感染小鼠分泌物具有感染性。     

Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus

Background Gallbladder carcinoma （GBC） has a high mortality rate,requiring synergistic anti-tumor management for effective treatment.The myxoma virus （MYXV） exhibits a modest clinical value through its oncolytic potential and narrow host tropism.Methods We performed viral replication assays,cell viability assays,migration assays,and xenograft tumor models to demonstrate that bone marrow-derived stem cells （BMSCs） may enhance efficiency of intravenous MYXV delivery.Results We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication,leading to an oncolytic effect.Furthermore,we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system.BMSCs failed to affect the growth of GBC cells,in terms of tumor volume and survival time.Finally,we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone,almost to the same extent as intratumoral injection of MYXV.Conclusion This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.     

A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9

Background: The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods: H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. ...     

Virus profile in children with acute respiratory infections with various severities in Beijing, China

Background Acute respiratory infection （ARI） is one of the most common infectious diseases in infants and young children globally.This study aimed to determine the virus profile in children with ARI presenting with different severities.Methods Clinical specimens collected from children with ARI in Beijing from September 2010 to March 2011 were investigated for 18 respiratory viruses using an xTAG Respiratory Viral Panel Fast （RVP Fast） assay.The Pearson chisquare analysis was used to identify statistical significance.Results Of 270 cases from three groups of ARI patients,including Out-patients,In-patients and patients in the intensive care unit （ICU）,viruses were detected in 176 （65.2％） specimens with the RVP Fast assay.The viral detection rate from the Out-patients group （50.0％） was significantly lower than that from the In-patients （71.1％） and ICU-patients （74.4％） groups.The virus distribution was different between the Out-patients group and the other hospitalized groups,while the virus detection rate and distribution characteristics were similar between the In-patients and ICU-patients groups.The coinfection rates of the Out-patients group,the In-patients group,and the ICU-patients group were 15.6％,50.0％ and 35.8％,respectively.In addition to respiratory syncytial virus （RSV） and adenovirus （ADV）,human rhinovirus （HRV） was frequently detected from children with serious illnesses,followed by human metapneumovirus （hMPV）,human bocavirus （HBoV） and coronaviruses.Parainfluenza virus 3 （PIV3） was detected in children with lower respiratory illness,but rarely from those with serious illnesses in the ICU-patient group.Conclusion In addition to so-called common respiratory viruses,virus detection in children with ARI should include those thoucht to be uncommon respiratory viruses,especially when there are severe ARI-related clinical illnesses.     

Pathogenesis and immunogenicity of an avian H9N2 influenza virus isolated from human

Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 (a reassortant of G1 and G9 viruses isolated from a female patient in 1999) in a mouse model of infection.Methods Mice were infected with increasing virus titers.Viral load in the lungs and trachea was determined by EID50 assay.Pulmonary histopathology was assessed by hematoxylin‐eosin staining.Anti‐HI antibody titers and T‐cell responses to viral HA were determined by ELISPOT and confirmed by flow cytome...     

HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects naïve to antiretroviral therapy

Background  The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs.

Methods  Tregs were defined as CD4⁺CD25⁺CD127^lo/- T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer.

Results  Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4⁺CD25⁺CD127^lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163, P=0.004) and negatively with CD4 T-cell counts (r=−0.4153, P <0.0001). In addition, significant associations between HLA-DR expression on CD4⁺CD25⁺CD127^lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4⁺ and CD8⁺ T cells were also identified.

Conclusion  HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

     

新型H7N9流感防控中的公共卫生问题与应对对策

2013年3月,在中国境内报道了首例因感染新型甲型H7N9流感病毒而致死的病例。除了病毒基因重组、重要氨基酸位点变异等病毒进化生物因素外,还存在影响人感染新型甲型H7N9流感的社会因素。目前中国尚存在活禽养殖过程不规范、交易市场管理混乱、从业人员卫生意识薄弱、居民自我防护措施不足等问题。这些因素通过增加人与生禽密切接触机会而促进流感病毒传播,增加人患禽流感的危险性。针对上述情况,在今后的流感防控工作中,应加强农、林、医等多部门联动机制的建设,进行高效的防控与监测;通过健康教育来提高居民的健康保护意识及风险意识。同时应该根据禽流感病毒进化监测数据加快科学研发流感疫苗进程。基于社会影响因素开展公共卫生预防应是今后降低人感染禽流感发生率的重要措施。     

H1N1流感与H7N9禽流感感染BALB/c小鼠发病特点初步研究

目的本实验旨在初步探讨A／shanghai／4664T（H7N9）和A／PuertoRico／8／34（H1N1）病毒感染BALB／c小鼠的发病特点,为H7N9致病机制与防治的研究提供数据支持。方法将同等剂量（5×10^3TCID50）流感病毒滴鼻感染BALB／c小鼠,分析其在感染后体重、肺指数、病毒载量和肺组织病理的变化情况。结果H1N1PR8感染组和H7N9感染组小鼠在7d内体重均持续减低,H1N1PR8组较H7N9组降低更为明显;在感染后3dH7N9组与PBS组肺指数无显著差异（P〉0．05）,但感染后7dH7N9组与PBS组相比显著增高（P〈0．05）;H1NlPR8组比H7N9组感染后3d肺指数显著增高（P〈0．05）,但感染后第7天无显著差异（P〉0．05）。H1N1PR8组和H7N9组病毒载量在感染后第3天均显著升高,但两组无显著差异;第7天两组病毒载量均有所降低,但H7N9组病毒载量显著高于H1N1PR8组（P〈0．05）。H1N1PR8在感染后3d主要病理变化为炎症细胞浸润和水肿,而H7N9组主要轻度炎症细胞浸润;在感染后7dH1N1PR8组可见大量炎症细胞浸润,出现大面积肺水肿;H7N9组表现为大量炎症细胞浸润。结论H7N9和H1N1PR8感染BALB／c小鼠均可发病,但发病特点有所差异,H7N9病毒对鼠的适应性比H1N1PR8差。     

新型禽源人流感病毒（H7N9）的小鼠感染模型和传播模型建立

目的建立新型禽源人流感病毒（H7N9）小鼠模型和可能的H7N9致病性和传播力研究。方法H7N9病毒感染小鼠,并与同居小鼠合笼,研究同居小鼠的临床指征变化,病毒复制情况,病毒在组织中的分布,以及病理变化。通过观察同居小鼠的发病情况等方面研究H7N9病毒在同笼小鼠中的传播能力。结果研究表明H7N9病毒能有效地感染小鼠并造成致死,可以通过直接接触传播感染小鼠并引起病理等改变。结论建立了H7N9小鼠模型,并对小鼠通过接触传播感染进行了初步研究,为深入研究传播力奠定了基础。     

乌鲁木齐市2017年2起人感染H7N9禽流感疫情分析

目的 对乌鲁木齐市2017年监测发现的2例人感染H7N9禽流感病例疫情进行调查分析,为人禽流感疫情防控提供有效参考依据。方法 对患者、密切接触者和活禽市场开展流行病学调查,采集病例呼吸道标本和外环境标本应用实时荧光定量PCR (real-time PCR)方法,检测甲型流感病毒及H7N9禽流感病毒特异的核酸片段,进行分析。结果 调查发现2例毫无关系患者同一天发热,先后检测出H7N9流感病毒核酸。2例患者均为男性,年龄相近,都有基础性疾病,经过救治,其中1例患者核酸检测转阴,症状消失救治成功。另1例患者核酸检测持续阳性,最终救治无效死亡。流行病学调查患者发病前7天均无活禽接触史,有相同的活禽宰杀点暴露史,经外环境采样,多份标本检测出禽流感病毒核酸。结论 2例感染H7N9禽流感病例感染来源于受H7N9病毒污染的活禽宰杀店的可能性较大,建议加强沿街商铺的规范管理和卫生消毒工作,规范禽类宰杀与销售。医疗机构加强流感样病例监测和不明原因肺炎监测是及时发现人禽流感病例的重要手段。     

Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

Background  Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.

Methods  Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n=6) pretreated with normal saline and the LPD group (n=6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.

Results  All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6) mmHg vs. (284.3±11.3) mmHg at 6 hours after ALI, P <0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg∙ml^-1∙g^-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg∙ml^-1∙g^-1 protein).

Conclusion  These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.

     

Anti-catabolic effect of caffeic acid phenethyl ester, an active component of honeybee propolis on bone loss in ovariectomized mice: a micro-computed tomography study and histological analysis

Background Osteoporosis （OP） is a common bone disease,which adversely affects life quality.Effective treatments are necessary to combat both the loss and fracture of bone.Recent studies indicated that caffeic acid phenethyl ester （CAPE） is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption.Therefore,this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography （CT） and histology.Methods Eighteen mice were prepared and evenly divided into three groups.The six mice in the sham＋PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period.Twelve mice were ovariectomized （OVX） to induce OP.Six of them in the OVX＋CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy.The other six OVX mice in OVX＋PBS group were treated with PBS.All the mice were sacrificed 4 weeks after ovariectomy.The tibias were bilaterally excised for micro-CT scan and histological analysis.The Mann-Whitney U test was used to test the statistical differences among groups.Results Bone loss occurred in OVX mice.Compared with the sham＋PBS group,mice in the OVX＋PBS group exhibited a significant decrease in bone mineral density （BMD,P ＜0.05）,bone volume fraction （BV/TV,P ＜0.01）,trabecular thickness （Tb.Th,P ＜0.05）,and trabecular number （Tb.N,P ＜0.01）,as well as a non-insignificant increase in the number of osteoclasts （N.Oc/B.Pm）.With CAPE treatment,the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation.Compared with the OVX＋PBS group,BV/TV in the OVX＋CAPE group was significantly increased by 33.9％ （P ＜0.05）.Conclusion CAPE therapy results in the protection of bone loss induced by OVX.     

Up-regulation of TIMP-2 expression promotes SHI-1 leukemic cells proliferation and infiltration in inmmunodeficiency mice

BackgroundMMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP-2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro.

MethodsA retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-1. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-treated nu/nu mice to investigate the infiltration ability feature in vitro.

ResultsThe expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over-expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice.

ConclusionOver-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.