目的观察电针对缺血性脑卒中大鼠神经行为学及脑组织结构的影响,探讨电针通过调控NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体途径改善缺血性脑卒中大鼠神经功能的...目的观察电针对缺血性脑卒中大鼠神经行为学及脑组织结构的影响,探讨电针通过调控NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体途径改善缺血性脑卒中大鼠神经功能的机制。方法36只健康雄性SD大鼠采用随机数字表随机分为假手术组12只及手术组24只,手术组大鼠采用Longa等改良线栓法制备大鼠脑缺血再灌注损伤(MCAO)模型。术后2 h行神经行为学评分,造模成功的大鼠再随机分为模型组及电针组。电针组予电针“曲池”“足三里”连续干预7 d,假手术组及模型组不做干预。干预完成后分别评估各组大鼠神经功能缺损情况,HE染色观察脑组织病理学变化,QPCR及Western blot法检测炎性小体相关蛋白NLRP3、ASC、Caspase-1的表达水平,ELISA检测各组大鼠血清IL-1β和IL-18炎性因子表达。结果与假手术组相比,模型组大鼠神经功能评分均显著提高,差异有高度统计学意义(P<0.01),脑组织缺血皮质区神经元胞体缩小变形,核固缩明显,大鼠脑组织缺血周围区炎性因子相关蛋白NLRP3、ASC、Caspase-1的mRNA及蛋白表达水平升高,差异有高度统计学意义(P<0.01),血清IL-1β和IL-18炎症因子表达增加,差异有高度统计学意义(P<0.01);经电针干预7 d后,电针组神经评分功能较模型组显著下降,差异有统计学意义(P<0.05),所见的病理损伤减少;炎性小体相关蛋白NLRP3、ASC、Caspase-1的表达下降,差异有统计学意义(P<0.05),且电针下调了血清IL-1β和IL-18的表达,差异有统计学意义(P<0.05)。结论电针“曲池”“足三里”可减轻缺血性脑卒中大鼠神经功能缺损症状,减少脑组织病理损伤,下调NLRP3、ASC、Caspase-1表达水平,其机制可能与调控NLRP3炎性小体途径抗细胞焦亡,减轻脑缺血再灌注损伤有关。展开更多
Objective: According to clinical phenotypic classification, there is a significant overlap of clinical features between different anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), and disease cl...Objective: According to clinical phenotypic classification, there is a significant overlap of clinical features between different anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), and disease classification based on ANCA subtype helps to differentiate clinical phenotypes. We investigated the clinical features and outcomes of patients based on ANCA serotype classification. Methods: Clinical and laboratory data were collected retrospectively. We compared clinical manifestations and organ involvement based on serotype. The risk factors for death and renal survival were investigated with univariate and multivariate Cox regression models. Results: Patients with MPO-ANCA were predominant, whose median age and lung involvement at diagnosis was higher than that of the PR3-ANCA patients. Compared to the AAV patients without renal involvement, those with renal involvement have older, anemia, low complement C3, and hypoproteinemia, more likely to have cardiovascular and abdominal involvement, and have less lung involvement. Multivariate Cox analysis revealed that age ≥ 65 years (HR = 2.611, p p = 0.019), BVAS ≥ 15 (HR = 1.943, p = 0.001), low C3 (HR = 1.696, p = 0.008), and hypoproteinemia (HR = 1.438, p = 0.044) were associated with mortality. SCR ≥ 500 μmol/L (HR = 13.583, p p = 0.020), low C3 (HR = 1.506, p = 0.049) were independent detrimental factors for renal survival, and immunosuppressive treatment was a protective factor for renal survival (HR = 0.523, p = 0.003). Conclusions: Clinical manifestations varied by AAV categories. Age, SCR, BVAS, low C3 and hypoproteinemia at diagnosis were independent predictors of mortality. BVAS, low C3, SCR at diagnosis and immunosuppressive treatment were independently related to renal survival in ANCA positive patients.展开更多
目的通过脂多糖(Lipopolysaccharide,LPS)诱导的脓毒症模型验证G蛋白偶联受体120(G-protein coupled receptor120,GPR120)基因对NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3...目的通过脂多糖(Lipopolysaccharide,LPS)诱导的脓毒症模型验证G蛋白偶联受体120(G-protein coupled receptor120,GPR120)基因对NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体及肺损伤的影响,并探索其调控分子机制。方法通过C57BL/6小鼠构建体内脓毒症模型,通过GPR120基因激动剂TUG891进行干预,验证GPR120基因对脓毒症小鼠肺损伤的保护作用;然后进行转录组测序,筛选差异信号通路,并在动物模型中验证NLRP3炎症小体及调控蛋白的差异表达。通过慢病毒转染构建GPR120基因过表达/低表达的Raw264.7单核巨噬细胞株,观察GPR120基因对NLRP3炎症小体的调控作用。结果与脓毒症组相比,LPS+TUG891组小鼠肺组织中包括cAMP通路基因在内的77个基因表达显著上调,37个基因表达下降。LPS组的GPR120水平较正常对照组显著降低,同时cAMP/PKA信号通路关键蛋白CREB及PKA表达减少,NLRP3、Caspase-1及IL-1β等炎症小体激活相关蛋白水平升高(P<0.01),予以TUG891处理后,组织内GPR120表达回升,cAMP/PKA信号通路重新被激活(P<0.01),NLRP3炎症小体蛋白活化程度下降(P<0.05)。体外实验中,LPS诱导的脓毒症可引起细胞增殖活性下降,GPR120基因在脓毒症巨噬细胞中表达减低(P<0.001),通过干预GPR120基因表达,证实GPR120基因可负性调控NLRP3炎症小体的活化程度及细胞炎症反应(P<0.01)。结论脓毒症中GPR120基因的激活可通过抑制NLRP3炎症小体的活化,减轻脓毒症的炎症反应及肺损伤。展开更多
The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between China and Europe.It pioneers the use of X-ray imaging technology...The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between China and Europe.It pioneers the use of X-ray imaging technology to perform large-scale imaging of the Earth’s magnetosheath and polar cusp regions.It uses a high-precision ultraviolet imager to image the overall configuration of the aurora and monitor changes in the source of solar wind in real time,using in situ detection instruments to improve human understanding of the relationship between solar activity and changes in the Earth’s magnetic field.The SMILE satellite is scheduled to launch in 2025.The European Incoherent Scatter Sciences Association(EISCAT)-3D radar is a new generation of European incoherent scatter radar constructed by EISCAT and is the most advanced ground-based ionospheric experimental device in the high-latitude polar region.It has multibeam and multidirectional quasi-real-time three-dimensional(3D)imaging capabilities,continuous monitoring and operation capabilities,and multiple-baseline interferometry capabilities.Joint detection by the SMILE satellite and the EISCAT-3D radar is of great significance for revealing the coupling process of the solar wind–magnetosphere–ionosphere.Therefore,we performed an analysis of the joint detection capability of the SMILE satellite and EISCAT-3D,analyzed the period during which the two can perform joint detection,and defined the key scientific problems that can be solved by joint detection.In addition,we developed Web-based software to search for and visualize the joint detection period of the SMILE satellite and EISCAT-3D radar,which lays the foundation for subsequent joint detection experiments and scientific research.展开更多
Background and objectives: Breast Imaging Reporting and Data System in Category 3 (BIRADS-3) includes probably benign lesions which need a short-term imaging follow-up. However, in our context, the lesions graded BIRA...Background and objectives: Breast Imaging Reporting and Data System in Category 3 (BIRADS-3) includes probably benign lesions which need a short-term imaging follow-up. However, in our context, the lesions graded BIRADS-3 remain insufficiently evaluated. We therefore conducted this study to assess the cancer occurrence and associated factors in BIRADS-3 lesions during the follow-up in order to propose an adaptation of the management for lesions in this category in our setting. Patients and methods: A retrospective longitudinal study of patients with lesions initially classified as BIRADS-3 and who realised each at least one additional imaging check-up between January 2014 and December 2022 in five Yaoundé hospitals. All clinical and imaging data were analysed using SPSS<sup>®</sup> 21.0 software with a significant p-value Results: Patients were aged 13 to 73 (33.0 ± 13.4) years, with a history of breast mass (315 cases;79.7%), breast pain (25 patients;6.3%), nipple discharge (20 patients;5.1%) or past family history of breast cancer (25 cases;6.3%). The most common baseline abnormalities were mammogram opacities (64.8%) and microcalcifications (48.6%), whereas initial breast ultrasound showed solid masses (77.0%) and cystic lesions (11.1%). Compliance with imaging appointment periods was low with only 23.9% of all patients performing an imaging control at the scheduled moment. During the follow-up, 115 patients (29.1%) were upgraded to BIRADS-4 and histology performed revealed 43 cancers (10.9% of overall initial BIRADS-3 sample). The presence of malignancies was associated to age above 40 years (p = 0.0001) and to the presence of nipple discharge (p = 0.0375). Conclusion: The frequency of malignancies among initial BIRADS-3 lesions in our series is higher than that described in the guidelines. This study highlights the need to be more proactive in the management of BIRADS-3 lesions in our setting as the compliance with follow-up is low. So, biopsy should be considered as an alternative to long-term follow-up for patients above 40, non-compliant with imaging check-ups and presenting with nipple discharge.展开更多
文摘Objective: According to clinical phenotypic classification, there is a significant overlap of clinical features between different anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), and disease classification based on ANCA subtype helps to differentiate clinical phenotypes. We investigated the clinical features and outcomes of patients based on ANCA serotype classification. Methods: Clinical and laboratory data were collected retrospectively. We compared clinical manifestations and organ involvement based on serotype. The risk factors for death and renal survival were investigated with univariate and multivariate Cox regression models. Results: Patients with MPO-ANCA were predominant, whose median age and lung involvement at diagnosis was higher than that of the PR3-ANCA patients. Compared to the AAV patients without renal involvement, those with renal involvement have older, anemia, low complement C3, and hypoproteinemia, more likely to have cardiovascular and abdominal involvement, and have less lung involvement. Multivariate Cox analysis revealed that age ≥ 65 years (HR = 2.611, p p = 0.019), BVAS ≥ 15 (HR = 1.943, p = 0.001), low C3 (HR = 1.696, p = 0.008), and hypoproteinemia (HR = 1.438, p = 0.044) were associated with mortality. SCR ≥ 500 μmol/L (HR = 13.583, p p = 0.020), low C3 (HR = 1.506, p = 0.049) were independent detrimental factors for renal survival, and immunosuppressive treatment was a protective factor for renal survival (HR = 0.523, p = 0.003). Conclusions: Clinical manifestations varied by AAV categories. Age, SCR, BVAS, low C3 and hypoproteinemia at diagnosis were independent predictors of mortality. BVAS, low C3, SCR at diagnosis and immunosuppressive treatment were independently related to renal survival in ANCA positive patients.
文摘目的通过脂多糖(Lipopolysaccharide,LPS)诱导的脓毒症模型验证G蛋白偶联受体120(G-protein coupled receptor120,GPR120)基因对NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体及肺损伤的影响,并探索其调控分子机制。方法通过C57BL/6小鼠构建体内脓毒症模型,通过GPR120基因激动剂TUG891进行干预,验证GPR120基因对脓毒症小鼠肺损伤的保护作用;然后进行转录组测序,筛选差异信号通路,并在动物模型中验证NLRP3炎症小体及调控蛋白的差异表达。通过慢病毒转染构建GPR120基因过表达/低表达的Raw264.7单核巨噬细胞株,观察GPR120基因对NLRP3炎症小体的调控作用。结果与脓毒症组相比,LPS+TUG891组小鼠肺组织中包括cAMP通路基因在内的77个基因表达显著上调,37个基因表达下降。LPS组的GPR120水平较正常对照组显著降低,同时cAMP/PKA信号通路关键蛋白CREB及PKA表达减少,NLRP3、Caspase-1及IL-1β等炎症小体激活相关蛋白水平升高(P<0.01),予以TUG891处理后,组织内GPR120表达回升,cAMP/PKA信号通路重新被激活(P<0.01),NLRP3炎症小体蛋白活化程度下降(P<0.05)。体外实验中,LPS诱导的脓毒症可引起细胞增殖活性下降,GPR120基因在脓毒症巨噬细胞中表达减低(P<0.001),通过干预GPR120基因表达,证实GPR120基因可负性调控NLRP3炎症小体的活化程度及细胞炎症反应(P<0.01)。结论脓毒症中GPR120基因的激活可通过抑制NLRP3炎症小体的活化,减轻脓毒症的炎症反应及肺损伤。
基金supported by the Stable-Support Scientific Project of the China Research Institute of Radio-wave Propagation(Grant No.A13XXXXWXX)the National Natural Science Foundation of China(Grant Nos.42174210,4207202,and 42188101)the Strategic Pioneer Program on Space Science,Chinese Academy of Sciences(Grant No.XDA15014800)。
文摘The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between China and Europe.It pioneers the use of X-ray imaging technology to perform large-scale imaging of the Earth’s magnetosheath and polar cusp regions.It uses a high-precision ultraviolet imager to image the overall configuration of the aurora and monitor changes in the source of solar wind in real time,using in situ detection instruments to improve human understanding of the relationship between solar activity and changes in the Earth’s magnetic field.The SMILE satellite is scheduled to launch in 2025.The European Incoherent Scatter Sciences Association(EISCAT)-3D radar is a new generation of European incoherent scatter radar constructed by EISCAT and is the most advanced ground-based ionospheric experimental device in the high-latitude polar region.It has multibeam and multidirectional quasi-real-time three-dimensional(3D)imaging capabilities,continuous monitoring and operation capabilities,and multiple-baseline interferometry capabilities.Joint detection by the SMILE satellite and the EISCAT-3D radar is of great significance for revealing the coupling process of the solar wind–magnetosphere–ionosphere.Therefore,we performed an analysis of the joint detection capability of the SMILE satellite and EISCAT-3D,analyzed the period during which the two can perform joint detection,and defined the key scientific problems that can be solved by joint detection.In addition,we developed Web-based software to search for and visualize the joint detection period of the SMILE satellite and EISCAT-3D radar,which lays the foundation for subsequent joint detection experiments and scientific research.
文摘Background and objectives: Breast Imaging Reporting and Data System in Category 3 (BIRADS-3) includes probably benign lesions which need a short-term imaging follow-up. However, in our context, the lesions graded BIRADS-3 remain insufficiently evaluated. We therefore conducted this study to assess the cancer occurrence and associated factors in BIRADS-3 lesions during the follow-up in order to propose an adaptation of the management for lesions in this category in our setting. Patients and methods: A retrospective longitudinal study of patients with lesions initially classified as BIRADS-3 and who realised each at least one additional imaging check-up between January 2014 and December 2022 in five Yaoundé hospitals. All clinical and imaging data were analysed using SPSS<sup>®</sup> 21.0 software with a significant p-value Results: Patients were aged 13 to 73 (33.0 ± 13.4) years, with a history of breast mass (315 cases;79.7%), breast pain (25 patients;6.3%), nipple discharge (20 patients;5.1%) or past family history of breast cancer (25 cases;6.3%). The most common baseline abnormalities were mammogram opacities (64.8%) and microcalcifications (48.6%), whereas initial breast ultrasound showed solid masses (77.0%) and cystic lesions (11.1%). Compliance with imaging appointment periods was low with only 23.9% of all patients performing an imaging control at the scheduled moment. During the follow-up, 115 patients (29.1%) were upgraded to BIRADS-4 and histology performed revealed 43 cancers (10.9% of overall initial BIRADS-3 sample). The presence of malignancies was associated to age above 40 years (p = 0.0001) and to the presence of nipple discharge (p = 0.0375). Conclusion: The frequency of malignancies among initial BIRADS-3 lesions in our series is higher than that described in the guidelines. This study highlights the need to be more proactive in the management of BIRADS-3 lesions in our setting as the compliance with follow-up is low. So, biopsy should be considered as an alternative to long-term follow-up for patients above 40, non-compliant with imaging check-ups and presenting with nipple discharge.
