Marburg virus (MARV) is a member of the Filoviridae family and belongs to a non-segmented, single-strand and negative-sense RNA virus.Since the first discovery of virus in 1967, infections have broken out 14 times, causing the infection of 588 people and 482 deaths.The mortality is up to 82%.Marburg virus results in multiple organ infections , severe hemorrhagic fever and death .Currently, there are no available licensed vaccines or post-exposure treatment , but the vaccines have proved effective in experimental animals .This review briefly summarizes the structure , infection mechanism and the progress in vaccines of this virus .

Objective A liver metastasis model of human primary malignant lymphoma of small intestine was reproduced in nude mice in an attempt to provide an ideal animal model for elucidating the mechanism of liver metastasis of primary small intestinal lymphoma.Methods A piece of surgically obtained liver metastatic tissue of small intestinal lymphoma was implanted into the mucous membrane of small intestine in nude mice to reproduce the model.After metastasis of this tumor to the liver occurred,a portion of the metastais was transplanted into the mucous membrane of small intestine of another nude mouse.This process was repeated 4 times in order to obtain a cell line with the characteristics of high malignant lymphoma metastasis to liver.The survival rate of the experimental animals,regional invasion rate and metastasis rate were observed,and the morphological characteristics(light microscopy,electron microscopy and immunohistochemistry),karyotype analysis and DNA content of the neoplastic cells were also determined.Results A liver metastasis model of human primary malignant lymphoma of small intestine in nude mice(termed HSIL-0402)was successfully reconstructed,by repeated implantation of liver metastatic tumor in vivo.Histopathology showed HSIL-0402 tumor was a high grade non-Hodgkin's lymphoma.Immunohistology showed the cells were CD19,CD20,CD45 and CD79a positive,but negative for CD3 and CD7.The modal number of chromosome was between 56-69.DNA index(DI)was 1.61?0.37,which showed heteroploid.So far,HSIL-0402 had been maintained for 27 passages in nude mice,exhibiting 100% of transplantability,liver metastatic rate,and resuscitation rate after liquid nitrogen cryopreservation.Lymph node metastasis and celiac seeding occurred in 67.4% and 61.7% of a total of 156 observed animals.The HSIL-0402 model displayed various manifestations reminiscent of highly metastatic invasive behavior in nude mice,including invasive growth,hematogenous metastasis,lymph node metastasis and celiac seeding.Conclusion The present study successfully re-established a spontaneous liver metastasis model of human primary malignant lymphoma of small intestine in nude mice,HSIL-0402,which provides an ideal animal model for the researches on biological mechanism of liver metastasis and anti-metastasis therapy of human primary small intestinal lymphoma.

to establish the human malignant lymphoma model in nude mice, orthotopic transplantation of histologically intact gastric lymphoma tissue from 11 patients was implanted into gastric submucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electronic microscopy, and immunohistochemistry. Two strains screened from 11 cases of human gastric lymphoma were the high metastasis model (HGL HMN 1)and the in situ model of human gastric lymphoma (HGL HMN 2) passaged in vivo for the 36th and 27th generations respectively. 329 nude mice were transplanted. Since the 3rd generation, the tumor transplantation growth rate and the resuscitation rate from liquid nitrogen were 100% .Lymph node metastasis, blood metastasis, and seeding metastasis were present. The transplanted tumors were similar to the original human malignant lymphoma in histopathological, ultrastructure features, DNA content and chromosomal karyatype. Its spontaneous growth occurred in the stomach of the nude mice,accompanied by destructive infiltration of every tissue layer of the stomach wall. Its invasion and metastasis simulated integrally the clinic process of human malignant lymphoma. These models can be used to study the etiology, invasion, metastasis and experimental treatment of human malignant lymphoma.

Objective To replicate an ideal animal model for exploring pathogenesis and experimental treatment of malignant lymphoma of small intestine. Methods Fresh lymphoma tissues derived from primary lesion and liver metastasis of malignant lymphoma of human small intestine obtained during operation were respectively transplanted into mucosa of small intestine and subcutaneous space in the interscapular region in nude mice. Tumorigenicity, invasion and metastasis of transplanted tumors were observed. Morphology (light microscopy, electron microscopy and immunohistochemistry), karyotype analysis, DNA quantitative assay (FCM) were also studied. Results From five patients of malignant lymphoma of small intestine, tumor tissue from 3 patients was successfully transplanted. According to the new classification of the World Health Organization, a strain of high metastatic model of orthotopically transplanted malignant lymphoma in nude mice (HSIL-0101) and another of subcutaneously transplanted highly metastatic model were reproduced from the same human neoplasm (non-Hodgkin B cell type); orthotopically Pathological study showed that the tumor was high-grade large B-cell lymphoma. Histochemitry showed that it was CD19, CD20, CD22 and CD45 positive, and CD3 and CD7 negative. The number of chromosome is ranged from 55 to 59; DI (DNA Index) was 1.47～1.61 (ie, heteroploid). HSIL-0101 and HSIL-0102 had been passaged for 32 and 38 generations in nude mice separately. 357 nude mice were transplanted. Rate of growth of neoplasm transplantation and resuscitation rate of liquid nitrogen cryopreservation were both 100%. In HSIL-0101, metastasis rate of liver and lymph node was 100%. In HSIL-0102, metastasis rate of liver was 63.5% and metastasis rate of lymph node was 62.7%. Transplanted tumors invasively grew in small intestine and subcutaneous region of nude mice. Blood metastasis was found (liver and spleen metastases). There were also lymph metastasis and seeding metastasis in the peritoneal cavity. Conclusions The study first successfully established spontaneous high metastasis models of malignant lymphoma of human small intestine in nude mice by orthotopic and subcutaneous transplantation. HSIL-0101 and HSIL-0102 could be used to carry out the research on pathogenesis, invasion, metastasis, and experimental therapy of malignant lymphoma of small intestine.

Objective To provide an experimental tool for explo ri ng pathogenesis and experimental treatment strategies for primary lymphoma of th e liver. Methods Histologically intact lymphoma tissues from pa tients with primary lymphoma of the liver were transplanted into hepatic parench yma of nude mice. Tumorgenecity, invasion, metastasis, morphological characteris tics(light microscopy, electron microscopy and immunohistochemistry), serologica l test(AFP, HBsAg and LDH), karyotype analysis and DNA content of orthotopically transplanted tumors were studied. Results Orthotopically trans planted model of human primary malignant lymphoma of the liver in nude mice(desi gnated as HLBL-0102) was successfully reproduced. Histopathology of transplante d tumors showed primary lymphoma of the liver(non-Hodgkin's, B cell). The cells were positive for CD19,CD20,CD45RO and CD79a, but negative for CD3 and CD7. Ser ological tests showed that the serum was AFP negative and HBsAg positive, and t he concentration of LDH was 1267.5U/L. The number of chromosome was between 55 and 59. DNA index(DI) was 1.57~1.61(i.e. heteroploid). So far, the strain HLB L-0102 has grown for 3 years and been passaged for 37 generations in nude mice. Altogether 283 nude mice were used for transplantation. The growth rate and res uscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. The transplanted tumors autonomoasly and invasively grew in the live r of nude mice, damaging adjacent liver tissues, bile ducts, and veins in the po rtal area. There was no involvement of other tissues and organs or distal lymph nodes. Orthotopically transplanted tumors were consistent in histopathological a nd ultrastructural features, DNA content and chromosomal karyotype with the orig inal human tumor. Conclusions The study is the first attempt to successfully reproduce orthotopically transplantation model of human primary ma lignant lymphoma of the liver in nude mice. HLBL-0102 completely replicates th e natural clinical process of primary lymphoma of the liver, and provides an ide al animal model for further research on the biology and experimental therapeutic strategies of primary lymphoma of the liver.

Objective To reproduce high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation, and to investigate their biologic features. Methods Histologically fresh lymphoma tissues from primary and liver metastatic lesions of human primary colorectal lymphoma obtained during operations were transplanted into colorectal mucosa of nude mice. Tumorgenecity, invasion, metastasis, morphology (light microscopy, electron microscopy and immunohistochemistry), karyotype analysis and DNA content of the orthotopically transplanted tumors were studied. Results According to the new WHO classification of malignant lymphoma, a strain of liver metastasis model of human primary colonic lymphoma (non-Hodgkin's, B cell) in nude mice by orthotopic transplantation (HCBL-0301), and a strain of high metastasis model of human primary rectal lymphoma (non-Hodgkin's, B cell) in nude mice by orthotopic transplantation (HRBL-0302) were successfully screened from four cases of human primary colorectal lymphoma. Histopathology of transplanted tumors showed high grade non-Hodgkin's large B cell lymphoma. The cells were positive for CD19, CD20, CD22 and CD45, but negative for CD3 and CD7. The number of chromosome was between 55 and 69. DNA index (DI) was 1.59~1.71 (i.e. heteroploid). So far, HCBL-0301 and HRBL-0302 had been passaged for 31 and 27 generations in nude mice, respectively, and transplantation was successful in 326 nude mice. Since the third generation, both the growth rate of transplantation and rate of resuscitation after being thawed from liquid nitrogen cryopreservation were 100%. In HCBL-0301, metastasis to the right lobe of liver was most common and metastatic rate was 100%; additionally, rates metastasis to of lymph node and peritoneal seeding were 67.4%. In HRBL-0302, metastasis to the left and right lobes of liver was most common with metastasis rate of 63.7%, and rates of metastasis to lymph node and peritoneal seeding were 56.4%. Transplanted human primary colorectal lymphoma could autonomously and invasively grow in the colorectum of nude mice, with occurrence of hematogenic, lymph node and implantation metastases. Conclusions The study successfully replicated high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation. HCBL-0301 and HRBL-0302 models can be used in the research on pathogenesis, mechanism of invasion and metastasis and experimental therapy of human primary colorectal lymphoma.

Objective Angiotensin Ⅱ (Ang Ⅱ ) contributes to modulating blood pressure by stimulation of Ang Ⅱ AT1 receptors. We devised a rat transient middle cerebral artery occlusion (MCAO) model to assess whether oxidative damage is decreased after pretreatment with Angiotensin Ⅱ AT1 receptor blocker (ARB). Methods After 2 weeks pretreatment with ARB 0. 5 and 1 mg/kg, the male Wister rats were subjected to 2 h middle cerebral artery occlusion (MCAO). At 24 h, the lumen diameter of middle cerebral artery, the plasma level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and HIF-1 a levels were recorded and compared. Results After pretrcatment with ARB 0.5 and 1 mg/kg, blood pressure did not significantly change compared with that of controls. In the group of candesartan at 1 mg/(kg· day), the lumen diameter was significantly increased compared to that in control group [(86.0±5.0) μm vs. (69.0± 2.1) μm; P<0. 01, n = 6- 8]. The plasma 8-OHdG levels of ARB pretreatment groups were decreased. In immunohistochemical findings, 8-OHdG- and HIF-1α-containing cells in ARB pretreatment groups were decreased. Conclusion Brain ischemia and oxidative damage can be reversed by AT1 receptor blockade in normotensive rats after transient cerebral artery occlusion.

Objective Angiotensin Ⅱ (Ang-Ⅱ) increases NADPH oxidase activity and stimulates the production of reactive oxygen species (ROS) including superoxide anion through Ang Ⅱ AT1-receptor (AT1-R) activation. ROS is involved in various pathological processes in brain ischemia. We investigated whether the AT1-R blocker (ARB) candesartan can protect normotensive rats against brain ischemia. Methods After 2-week pretreatment with candesartan, rats were subjected to 2 hours middle cerebral artery occlusion-reperfusion (MCAO-R) and 24 hours later, the infarct volume, iNOS, and eNOS mRNA in the internal carotid artery was recorded and compared. Results Candesartan pretreatment reduced cerebral ischemia and oxidative brain damage after MCAO-R in normotensive rats, resulting in a decreased cortical infarct volume [0.5 mg/kg candesartan, (46.8±13.2)mm3; 1.0 mg/kg candesartan, (19.3±15.3)mm3 vs. control, (111.7±14.3)mm3; P<0.05, P<0.01, respectively]. Candesartan pretreatment increased the eNOS mRNA level in the internal carotid artery. Conclusion In normotensive rats exposed to MCAO-R, candesartan protectes against brain ischemia. This effect may represent a significant therapeutic advantage and may induce end-organ protection even at normal blood pressure.

Humans ; Lung Neoplasms ; etiology ; Metallurgy ; Occupational Exposure

Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant melanoma in the small intestine.Methods Fresh tissue of lung metastatic lesions from patients with malignant melanoma of the smallintestine were transplanted into mucosa of the small intestine in nude mice.After 4 times of screening.the tissue of the lung metastatic lesions from the nude mice were transplanted into the small intestine of additionat nude mice.Tumorgenecity and metastasis of transplanted tumors were observed,and were analyzed by morphology,karyotype and flow cytometry.Results A lung metastatic model of human primary malignant melanoma of the small intestine in nude mice was successfully constructed and named HSIM-0601.Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Immunohistochemical straining of S-100 and HMB-45 were positive.The number of chromosome was between 57 and 59.DNA index was 1.49.HSIM-0601 was passed for 26 generations.A total of 173 nude mice were used for tumor transplantation.The growth rate of the transplanted tumors and resuscitation rate of liquid nitrogen cryopreservation were both 100%.In HSIM-0601.lung metastasis rate was 100%(173/173)and lymph node metastasis rate was 61.3%(106/173).Conclusions The HSIM-0601 successfully mimics the natural clinicopathologic course of patients with primary small intestinal melanoma,and provides an ideal animal model for research on pathogenesis,metastasis and experimentM therapy of malignant lymphoma in the small intestine.