反义CD40RNA对EB病毒转化的B细胞CD40分子表达和增殖能力的影响

目的 :探讨瞬时表达的反义CD4 0RNA ,对EB病毒转化的健康人B细胞膜表面CD4 0分子表达和增殖能力的影响。方法 :应用T A克隆技术和亚克隆技术 ,构建人反义CD4 0RNA的真核表达载体pcDNA3/CD4 0 ,并以其转染本室建立的EB病毒转化的健康人B细胞。应用流式细胞仪 (FACS) ,检测B细胞膜上CD4 0分子表达的变化。应用MTT比色法检测反义CD4 0RNA对B细胞增殖能力的影响。结果 :与转染空载体pcDNA3组相比 ,转染pcDNA3/CD4 0细胞上CD4 0分子的表达降低 (P<0 .0 1) ,其增殖能力明显降低 (P <0 .0 1)。结论 :反义CD4 0RNA技术 ,可作为有效的免疫调控手段。CD4 0基因本身在细胞的生长代谢中也起着重要作用     

CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide

Although deposition of amyloid beta-peptide (Abeta) as Abeta plaques involves activation of microglia-mediated inflammatory responses, activated microglia ultimately fail to clear Abeta plaques in the brains of either Alzheimer's disease (AD) patients or AD mouse models. Mounting evidence suggests that chronic microglia-mediated immune response during Abeta deposition etiologically contributes to AD pathogenesis by promoting Abeta plaque formation. However, the mechanisms that govern microglia response in the context of cerebral Abeta/beta-amyloid pathology are not well understood. We show that ligation of CD40 by CD40L modulates Abeta-induced innate immune responses in microglia, including decreased microglia phagocytosis of exogenous Abeta(1-42) and increased production of pro-inflammatory cytokines. CD40 ligation in the presence of Abeta(1-42) leads to adaptive activation of microglia, as evidenced by increased co-localization of MHC class II with Abeta. To assess their antigen-presenting cell (APC) function, cultured microglia were pulsed with Abeta(1-42) in the presence of CD40L and co-cultured with CD4(+) T cells. Under these conditions, microglia stimulate T cell-derived IFN-gamma and IL-2 production, suggesting that CD40 signaling promotes the APC phenotype. These data provide a mechanistic explanation for our previous work showing decreased microgliosis associated with diminished cerebral Abeta/beta-amyloid pathology when blocking CD40 signaling in transgenic Alzheimer's mice.     

Localization in situ of the co-stimulatory molecules B7.1, B7.2, CD40 and their ligands in normal human lymphoid tissue

Functional interactions between B and T lymphocytes are known to depend on the expression of co-stimulatory molecules B7.1/CD80, B7.2/CD86 and their counter-receptors CD28 and CTLA4, as well as CD40 and its ligand CD40L. To study the role of these molecules in situ, an immunohistochemical analysis was carried out on normal human lymphoid tissue. In the germinal centers (GC), B7.1 and B7.2 were differentially expressed. In the dark zone, centroblasts were predominantly B7.1⁺, while centrocytes in the light zone were B7-2⁺, resulting in reversed gradients of both markers in GC. Follicle mantle cells were negative for B7.1 and B7.2. Macrophages and interdigitating dendritic cells (IDC) in T cell zones both expressed B7.1 and B7.2. Moreover, clusters of B7.2⁺ T cells were demonstrated in interfollicular areas. Intrafollicular CD4⁺ T cells in GC, predominantly in the apical light zone, expressed CD28 and CTLA4, as did the majority of interfollicular T cells. CTLA4 showed a striking excentric cytoplasmic staining, which was also seen on T cells activated in vitro. CD40 was expressed on all B cells and more strongly on macrophages and IDC. Moreover, small clusters of T cells in a rim outside the GC showed CD40 expression. CD40L was expressed both on intrafollicular CD4⁺ T cells as well as on T cells in T cell zones. The differential distribution of co-stimulatory molecules in different compartments of normal human lymphoid tissue in situ indicates that these interactions play a distinctive role in different stages of B cell differentiation and in the immune response.     

Localized Sudeck's dystrophy and distal interphalangeal osteoarthritis of a finger: anatomicoradiologic study

After an injury to the right ring finger, a 44-year-old woman experienced pain in the distal interphalangeal joint. A subcutaneous mucoid cyst was noted near the joint. The x-ray films revealed no fracture but a narrowing of the joint space and a well-defined radiolucent area in the ulnar condyle of the middle phalanx. The biopsy specimen of this area excluded infection or tumor and revealed active osteogenic remodelling. These elements permitted a diagnosis of distal interphalangeal osteoarthritis that was associated with highly localized Sudeck's dystrophy (also called " parcellar algodystrophy"). This unusual case suggests the possibility that this dystrophy might be favored by an "osteoarthritic terrain" and might also play a role in the evolution of the osteoarthritis.     

The recovery of α-adrenoceptor function and binding sites after phenoxybenzamine

Summary The recovery of peripheral -adrenoceptor function and binding sites was studied in male New Zealand white rabbits after treatment with the irreversible adrenoceptor antagonist phenoxybenzamine. Phenoxybenzamine (5 mg/kg) was administered intravenously and the animals studied 30 min to 12 days later. Pressor dose response curves to intravenous phenylephrine, noradrenaline and guanabenz were constructed in vivo in conscious animals. The contractile response of abdominal aorta and renal artery to phenylephrine and noradrenaline was examined in vitro and the recovery of specific prazosin and clonidine binding to spleen membranes investigated in radioligand binding studies.The half life (t _1/2) for recovery of maximum pressor response in vivo ranged from 0.9±0.2 days for phenylephrine to 1.4±0.1 days for guanabenz. The t _1/2 for recovery of ED₅₀ was not significantly different to t _1/2 for recovery of maximum pressor response and ranged from 0.8±0.2 days for noradrenaline to 1.3±0.3 days for phenylephrine.Half life for recovery of maximum response and EC₅₀ in the isolated tissues was similar to that obtained in vivo for recovery of pressor responses and ranged from 0.4±0.1 days for the EC₅₀ of noradrenaline in the renal artery to 1.2±0.6 days for maximum response to phenylephrine in the abdominal aorta.The rate of recovery of specific clonidine binding did not differ significantly from the rate of recovery of pressor responses to the ₂-selective agonist guanabenz. t _1/2 for maximum number of specific clonidine binding sites, B _max was 1.6±0.9 days. However t _1/2 for recovery of specific prazosin binding was significantly longer than recovery of responses to phenylephrine and noradrenaline, t _1/2 for B _max was 3.6 ±0.1 day.     

改质炉高温炉管运行损伤及剩余寿命分析

对高温运行70000h至90000h改质炉炉管进行试验研究及材料损伤分析,结果表明,炉管的材料性能已严重劣化（脆化）,炉管的内外壁已有微小裂纹萌生,测定了炉管材料在950℃、各种应力水平下的断裂时间,根据时间-温度参数L-M公式,推测炉管的剩余寿命为8510h。     

Breast cancer in young women: Imaging and clinical course

The purpose of this study was to characterize presenting imaging findings in women younger than 40 diagnosed with invasive breast cancer in the context of pathology and clinical course. Retrospective chart and imaging reviews were performed in patients under 40 diagnosed with breast cancer between July 1, 2004, and December 31, 2013. Patient demographic, imaging, pathology, and clinical data were collected. Overall and recurrence-free survival were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were performed to identify factors associated with recurrence-free survival. Our study cohort consisted of 110 patients with invasive mammary carcinoma. One hundred one (91.8%) presented with a palpable mass. The mean size of all lesions on imaging was 3.5 cm ± 2.9 cm. Malignant calcifications were present in 54 (49.1%) cases. Imaging demonstrated multifocal or multicentric disease in 45 (40.9%) cases. Seventy four (67.3%) cancers were high grade. Luminal genomic subtypes were the most common (n = 61, 55.5%). At presentation, 4 (3.6%) patients had bilateral malignancy and 8 (7.3%) patients had distant metastatic disease. Ninety seven (88.2%) underwent neoadjuvant chemotherapy and 67 (60.9%) underwent radiation therapy. Seventy five (68.2%) of the patients underwent mastectomy. The restricted mean time to recurrence was 9.01 years (standard error 3.162 months). ER positivity was associated with compromised recurrence-free survival. The overall survival rate was 0.962 at 10 years. Young patients diagnosed with breast cancer typically present with advanced breast imaging findings and undergo aggressive treatment. Recurrence often occurs >5 years from diagnosis, and ER positive subtypes are at increased risk for recurrence.     

尿甲壳质酶蛋白-40对新生儿急性尿路感染的早期诊断价值及与其他指标相关性分析

目的探讨尿甲壳质酶蛋白40(YKL-40)对新生儿急性尿路感染(UTI)的早期诊断价值,并分析其与其他临床指标的相关性。方法选择2015年1月至2018年6月在本院就诊的疑似急性UTI患儿88例作为研究对象,取清洁中段尿10mL,放入带塞无菌试管中并在1h内送检.经细菌培养后进行成分分析。根据细菌培养结果将患儿分为对照组(细菌培养阴性49例)和观察组(细菌培养阳性39例),对比两组患者各临床指标。结果两组的血肌酐(Scr)和肾小球滤过率估计值(eGFR)比较.差异均无统计学意义(P>0.05),观察组的血沉(ESR)及C反应蛋白(CRP)明显高于对照组(P<0.05)。观察组患儿的尿YKL-40/尿肌酐(Cr)水平明显高于对照组患儿(P<0.05),对照组中脓尿阳性与阴性者YKL40/Cr水平比较,差异无统计学意义(P>0.05)。观察组中脓尿、血尿、蛋白尿、亚硝酸盐、肾积水及膀胱输尿管反流检查结果阳性与阴性者YKL40/Cr水平比较,差异均无统计学意义(P>0.05)。受试者操作特征(ROC)曲线分析结果显示尿YKL 40/Cr对UTI诊断截断值为123.25 pg/mg,曲线下面积(AUC)为.0.793,P=0.023,灵敏度为82.05%,特异度为90.04%。相关性分析结果显示YKL40/Cr与性别、体重指数(BMI)、ESR.eGFR、血尿、蛋白尿、肾积水及膀胱输尿管反流均不具有显著相关性(P>0.05),与出生天数、发烧持续时间呈显著负相关(r<0,P<0.05).与白细胞计数、CRP.脓.尿及亚硝酸盐阳性显著正相关(r>0,P<0.05)。结论尿YKL-40对新生儿急性UTI早期诊断具有较高的诊断价值,其水平与出生天数、发烧持续时间呈显著负相关,与白细胞计数、CRP、脓尿及亚硝酸盐阳性显著正相关。     

携带双自杀基因且可诱导敲除SV40T的逆转录病毒载体的构建与结构鉴定

目的构建携带双自杀基因且可诱导敲除SV40T的逆转录病毒载体,优化目前的肝细胞永生化。方法去除eGFP终止子taa的pSEB-HUS质粒为逆转录病毒基础质粒。先将SV40T及其启动子hEFH亚克隆至pSEB-HUS,再将LoxP位点插入至pSEB-SV40T质粒的抗性基因Blasticidin上游获得pSEB-LoxP-SV40T质粒。同时将CD自杀基因定向克隆至pSEB-HUS的eGFP下游;然后设计一段HSV-tk自杀基因引物,在上游引物的5′端加入方向一致的LoxP序列。PCR获得TK基因后,定向克隆至CD下游获得pSEB-CD-TK,最后将pSEB-CD-TK上的双自杀基因亚克隆至pSEB-LoxP-SV40T质粒上得到携带双自杀基因及SV40T的质粒。结果PCR及酶切鉴定均证实两个自杀基因及SV40T正确克隆至逆转录病毒质粒中,目的基因序列与GenBank报道一致,两个LoxP位点方向相同。结论成功构建携带双自杀基因且可诱导敲除SV40T的逆转录病毒载体。