Background: In the previous study, we established an ischemia-prone gerbil population(IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion(UCO)-induced ischemia in Mongoli...Background: In the previous study, we established an ischemia-prone gerbil population(IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion(UCO)-induced ischemia in Mongolian gerbils. However, if the characteristics of ischemia model in IG are the same as those in general gerbils(GG), and if the neurological symptoms are associated with the neurological insults in IG is still unclear.Methods: In the present study, we evaluated the UCO model in IG by analyzing neurological symptoms, neurological injury in the hippocampal CA1 region and compared with GG.Results: The data showed that the ratios of neurological symptom scores ≥ 2 in the IG and GG groups were 65.0% vs 30.0%, respectively, and were significantly different(P <.01).The neuronal damage following a UCO ischemic insult in the IG group was more severe compared to the GG group. There was a high correlation between the neurological insults' scale and the neurological symptom score in the IG and GG groups(r =.979 and.943 in the IG and GG groups, respectively). In animals with mild neurological symptom scores(2 and 3), the neuronal insults were significantly different between female and male gerbils in both IG and GG.Conclusion: Our findings suggest that IG population would likely be more advantageous to establish an ischemic model.展开更多
BACKGROUND The role of HER2 overexpression in rectal cancer is controversial.AIM To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer.METHODS Data from patients with locally advanced r...BACKGROUND The role of HER2 overexpression in rectal cancer is controversial.AIM To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer.METHODS Data from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected.A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy,followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients’HER2 expression status.Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed.Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status,and the differences between groups were verified using the log-rank test.RESULTS A total of 151 patients were enrolled in this study.A total of 27(17.9%)patients were ultimately confirmed to be HER2-positive.The follow-up duration ranged from 9 mo to 210 mo,with a median of 134 mo.Distant metastasis and local recurrence occurred in 60(39.7%)and 24(15.9%)patients,respectively.HER2 positivity was significantly associated with the pre-treatment lymph node stage(pre-N)(P=0.040),while there were no differences between HER2 status and age,sex,preoperative CEA levels(pre-CEA),T stage,and lympho-vascular invasion.In terms of prognosis,HER2 overexpression was correlated with distant meta stasis(P=0.002)rather than local recurrence(P>0.05).The multivariate analysis demonstrated that elevated pre-CEA[P=0.002,odds ratio(OR)=3.277,97.5%confidence interval(CI):1.543-7.163],post N(+)(P=0.022,OR=2.437,97.5%CI:1.143-5.308)and HER2(+)(P=0.003,OR=4.222,97.5%CI:1.667-11.409)were risk factors for distant metastasis.The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival(DFS)[hazard ratio:1.69(95%CI:0.91-3.14);P=0.048]and overall survival(OS)[1.95(1.05-3.63);P=0.0077].CONCLUSION HER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis,which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.展开更多
Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRN...Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells.Methods: Human umbilical vein endothelial cells (HUVECs) were culturedin vitro and arranged to harvest EMPs in two parts: the first part consisted of EMPcontrol and EMPhypoxia and the second part included EMPvehicle, EMPNC mimic, and EMPmiR-19b mimic. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student’st-test was used when two groups were compared.Results: Compared with EMPcontrol- and EMPhypoxia-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40,P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52,P < 0.01), the number of tube formations was markedly reduced by 70% in the EMPhypoxia group (P < 0.001)in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMPmiR-19b mimic was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed thatTGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression ofTGFβ2 in HUVECs was inhibited by treatment with EMPhypoxia and EMPmiR-19b mimic .Conclusions: MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.展开更多
基金Key Projects in the National Science&Technology Pillar Program,Grant/Award Number:2015BAI09B01
文摘Background: In the previous study, we established an ischemia-prone gerbil population(IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion(UCO)-induced ischemia in Mongolian gerbils. However, if the characteristics of ischemia model in IG are the same as those in general gerbils(GG), and if the neurological symptoms are associated with the neurological insults in IG is still unclear.Methods: In the present study, we evaluated the UCO model in IG by analyzing neurological symptoms, neurological injury in the hippocampal CA1 region and compared with GG.Results: The data showed that the ratios of neurological symptom scores ≥ 2 in the IG and GG groups were 65.0% vs 30.0%, respectively, and were significantly different(P <.01).The neuronal damage following a UCO ischemic insult in the IG group was more severe compared to the GG group. There was a high correlation between the neurological insults' scale and the neurological symptom score in the IG and GG groups(r =.979 and.943 in the IG and GG groups, respectively). In animals with mild neurological symptom scores(2 and 3), the neuronal insults were significantly different between female and male gerbils in both IG and GG.Conclusion: Our findings suggest that IG population would likely be more advantageous to establish an ischemic model.
基金Supported by Beijing Municipal Administration of Hospitals Incubating Program,No.PZ2020027Beijing Talent Incubating Funding,No.2019-4.
文摘BACKGROUND The role of HER2 overexpression in rectal cancer is controversial.AIM To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer.METHODS Data from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected.A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy,followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients’HER2 expression status.Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed.Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status,and the differences between groups were verified using the log-rank test.RESULTS A total of 151 patients were enrolled in this study.A total of 27(17.9%)patients were ultimately confirmed to be HER2-positive.The follow-up duration ranged from 9 mo to 210 mo,with a median of 134 mo.Distant metastasis and local recurrence occurred in 60(39.7%)and 24(15.9%)patients,respectively.HER2 positivity was significantly associated with the pre-treatment lymph node stage(pre-N)(P=0.040),while there were no differences between HER2 status and age,sex,preoperative CEA levels(pre-CEA),T stage,and lympho-vascular invasion.In terms of prognosis,HER2 overexpression was correlated with distant meta stasis(P=0.002)rather than local recurrence(P>0.05).The multivariate analysis demonstrated that elevated pre-CEA[P=0.002,odds ratio(OR)=3.277,97.5%confidence interval(CI):1.543-7.163],post N(+)(P=0.022,OR=2.437,97.5%CI:1.143-5.308)and HER2(+)(P=0.003,OR=4.222,97.5%CI:1.667-11.409)were risk factors for distant metastasis.The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival(DFS)[hazard ratio:1.69(95%CI:0.91-3.14);P=0.048]and overall survival(OS)[1.95(1.05-3.63);P=0.0077].CONCLUSION HER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis,which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.
基金grants from the National Natural Science Foundation of China (Nos.81770356, 81470473,and 81600340)and the Capital Health Research and Development of Special (No.2016-2-4083).
文摘Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells.Methods: Human umbilical vein endothelial cells (HUVECs) were culturedin vitro and arranged to harvest EMPs in two parts: the first part consisted of EMPcontrol and EMPhypoxia and the second part included EMPvehicle, EMPNC mimic, and EMPmiR-19b mimic. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student’st-test was used when two groups were compared.Results: Compared with EMPcontrol- and EMPhypoxia-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40,P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52,P < 0.01), the number of tube formations was markedly reduced by 70% in the EMPhypoxia group (P < 0.001)in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMPmiR-19b mimic was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed thatTGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression ofTGFβ2 in HUVECs was inhibited by treatment with EMPhypoxia and EMPmiR-19b mimic .Conclusions: MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.
