抗p21ras单克隆抗体在甲状腺乳头状癌中的免疫反应性研究

目的评价抗p21ras单克隆抗体（mAb）KGH-R1、KGH-R2、KGH-R3与原发性甲状腺乳头状癌及相应正常组织的免疫反应性,为该抗体的临床应用奠定基础。方法用本实验室制备的广谱抗p21ras mAb KGH-R1、KGH-R2、KGH-R3抗体,对30例甲状腺乳头状癌和30例周围正常甲状腺组织进行免疫组化染色,计算各样本的阳性细胞百分比和组织学评分（HSCORE）分值,确定这三种抗体对甲状腺乳头状癌及甲状腺正常组织免疫反应性的差异。结果抗p21ras单克隆抗体KGH-R1、KGH-R2、KGH-R3分别与70.00%（21/30）、76.67%（23/30）、60.00%（18/30）的甲状腺乳头状癌发生免疫反应,阳性样本的平均阳性细胞百分比分别为为81%、100%、68%,平均HSCORE评分分别为277.50分、272.50分、264.00分;分别与30.00%（9/30）、23.33%（7/30）、33.33%（10/30）的正常甲状腺组织发生免疫反应,阳性样本的平均阳性细胞百分比分别为7.75%、8.00%、10.20%,平均HSCORE评分分别为7.75分、8.00分、10.20分。结论这三种单克隆抗体在甲状腺乳头状癌中免疫反应性较强,而在正常甲状腺组织的免疫反应性较弱或呈阴性反应。因此,这三种单克隆抗体可进一步开发为治疗性抗体,用于原发性甲状腺乳头状癌的临床治疗。     

基于RIFLF标准的中老年开腹手术后急性肾损伤危险因素分析

目的 分析外科相关急性肾损伤影响因素.方法 纳入2006年4月～ 2011年1月开腹手术合并术后急性肾损伤(AKI)患者46例,均符合RIFLF标准,记录患者各项临床资料.以同期开腹腔手术未合并AKI患者为对照,分析术后AKI患者发生的危险因素.通过生存曲线分析术后AKI病死率与AKI分期关系.结果 (1)纳入开腹手术合并AKI患者46例,平均年龄(52.56±8.28)岁,其中既往有肾脏病史患者9例.按RIFLF分期示AKI Ⅰ期患者24例;AKIⅡ期患者15例,AKIⅢ期患者7例;(2)单因素分析结果显示两组病例间术前肌酐、蛋白尿、营养不良、血容量不足、肾脏病史例数有显著性差异(P＜0.05);(3)多因素分析结果显示急诊手术相对危险度(OR)为3.19,肾脏病史的OR为6.28;围手术期血容量不足OR为14.78;蛋白尿OR为2.21;术中失血超过1000 ml的OR为3.71,纳入方程有意义;(4)术后AKI生存曲线分析显示,AKI Ⅰ期、AKIⅡ、AKIⅢ期患者间病死率有显著性差异(P＜0.05).结论 外科开腹手术后AKI与多种因素相关,早期干预AKI发生是改善其预后的关键.     

Competitive inhibitors of the CphA metallo-beta-lactamase from Aeromonas hydrophila

Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with one zinc) either contain a thiol (and show less inhibition towards this subgroup than towards the dizinc members of B1 and B3) or are inactivators behaving as substrates for the dizinc family members. The present work reveals that certain pyridine carboxylates are competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner within the active site. Salts of these compounds are already available and undergoing biomedical testing for various nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases.     

The stem cell niches in bone

The stem cell niche is composed of a specialized population of cells that plays an essential role in regulating adult stem cell self-renewal and differentiation. In adults, osteoblasts, responsible for osteogenesis, and hematopoietic cells, responsible for hematopoiesis, are closely associated in the bone marrow, suggesting a reciprocal relationship between the two. It was recently discovered that a subset of osteoblasts functions as a key component of the HSC niche (namely, the osteoblastic niche), controlling HSC numbers. HSCs interact not only with osteoblasts but also with other stromal cells, including endothelial cells. Sinusoidal endothelial cells in bone marrow have been revealed as an alternative HSC niche called the vascular niche. In this Review we compare the architecture of these 2 HSC niches in bone marrow. We also highlight the function of osteoblasts in maintaining a quiescent HSC microenvironment and the likely role of the vascular niche in regulating stem cell proliferation, differentiation, and mobilization. In addition, we focus on studies of animal models and in vitro assays that have provided direct insights into the actions of these osteoblastic and vascular niches, revealing central roles for numerous signaling and adhesion molecules. Many of the discoveries described herein may contribute to future clinical treatments for hematopoietic and bone-related disorders, including cancer.     

继发于恶性肿瘤骨髓纤维化症47例临床资料分析

目的探讨继发性骨髓纤维化(secondarymyelofibrosis,SMF)患者的临床及骨髓病理学特点。方法对1995年～2004年同济医院确诊的47例继发性骨髓纤维化患者的临床表现、血片和骨髓象的细胞学表现及骨髓活检进行了回顾性研究,同时对不同疾病SMF程度与巨核细胞数的关系作了相关分析。结果骨髓转移癌常伴有SMF,易致骨髓穿刺干抽或稀释。急性淋巴细胞性白血病(ALL)或多发性骨髓瘤(MM)常伴SMF,骨髓象不易确诊,骨髓活检常能提供确诊的依据。各原发疾病之间MF程度没有统计学差异,而且MF程度与巨核细胞数没有明显相关性。结论当骨髓穿刺表现为“干抽”或疑为稀释、增生低下时,要考虑可能合并SMF,则应做骨髓活检,有助于对骨髓转移癌、ALL、MM、恶性淋巴瘤等疾病的诊断。     

Modulation of the poliovirus receptor expression in malignant lymphocytes by epigenetic alterations

Malignant lymphocytes are characterized by their low expression of poliovirus receptor (PVR), ligand for the activating natural killer (NK) cell receptors, which may explain their insensitivity toward NK cell-based therapeutic approaches. Here, we have studied the mechanism of this defective expression of PVR. We demonstrated that the characterization of NK-insensitive cell lines was of low expression of PVR in both mRNA and surface levels, and that PVR of RAJI cells able to resist NK cells has hypermethylated promoter-associated CpG islands. After treating with 5-azacytidine (5-AZA) (ie, hypomethylation agent) and suberoylanilide hydroxamic acid (SAHA) (ie, histone deacetylase inhibitor), respectively or simultaneously, the abnormal epigenetic status became partly reversed, and the mRNA and surface expression of PVR restored. The expression restoration of the gene enhanced susceptibility of RAJI cells to NK cells but, when the RAJI cells were incubated with the specific blocking antibody for PVR's receptor, the enhanced susceptibility would diminish. Patients with acute myeloid leukemia expressed higher PVR than patients with acute lymphoblastic leukemia in both mRNA and surface levels. Epigenetic modulation of hypermethylation and histone deacetylase is involved in repressing PVR expression in malignant lymphocytes resistant to NK cells.     

对输注多巴胺病人实施静脉保护的做法和用药护理

在重症监护病房,多巴胺是维持血压的首选药物.由于药物对局部血管刺激性强,药物浓度过大,应用时间维持较长等因素,使用中局部血管反应也较大,常规用量也可引起局部皮肤苍白、发红,甚至坏死[1],发生局部并发症甚至引发护理纠纷情况时有报道.我科于2004年7月-2007年7月,接受各类心血管疾病使用多巴胺治疗病人共41例,通过采用合理的静脉保护,无一例局部并发症发生,现报道如下.     

Predictive role of CHADS2 and CHA2DS2-VASc scores on stroke and thromboembolism in patients without atrial fibrillation: a meta-analysis

Objective: CHA₂DS₂-VASc is the extension of the CHADS₂ score developed by Birmingham 2009. This risk stratification schema is often used in clinical setting when considering additional risk factors for developing stroke in AF patients. However, its role in the non-AF population is unknown. This study was designed to evaluate the accuracy of the CHADS₂ and the CHA₂DS₂-VASc scoring systems.

Methods: Studies designed for CHADS₂ and CHA₂DS₂-VASc score in stratifying the risks for stroke development in non-AF patients were included.

Results: Among the 114 studies identified, six trials were chosen finally and included for meta-analysis. The pooled diagnostic odds ratio (DOR) for CHADS₂ and CHA₂DS₂-VASc was 2.86 (95% CI =1.83–4.28) and 2.80 (95% CI =1.83–4.28), respectively. CHA₂DS₂-VASc score was of better sensitivity than CHADS₂ score (0.920 vs. 0.768). However, both scores were showed to have inherent heterogeneity and poor specificity.

Conclusions: Though having good diagnostic accuracy, the clinical application of the CHADS₂ and CHA₂DS₂-VASc scores in predicting risk of stroke development in non-AF patients still needs further validation.

• Key message

• The overall diagnostic accuracy of CHADS₂ and CHA₂DS₂-VASc in stroke-risk stratification was good in patients with non-atrial fibrillation.

     

丙戊酸对致死性失血性休克犬器官功能和预后的影响

目的 探讨组蛋白去乙酰化酶抑制剂丙戊酸(VPA)对致死性失血性休克犬器官功能和预后的影响.方法 20只成年雄性Beagle犬,采用颈总动脉放血(按全身血容量的42%计算)制备失血性休克模型.将模型犬按随机数字表法分为休克对照组和VPA治疗组,每组10只.VPA治疗组于失血后1.5 h静脉注射(静注)VPA 100 mg/kg(溶于20 ml生理盐水),休克对照组在失血后24 h内静注20 ml生理盐水;失血后24 h起两组犬均实施延迟静脉补液.在非麻醉状态下测定犬失血前(0 h)和失血后不同时间点平均动脉压(MAP)及血浆丙氨酸转氨酶(ALT)、肌酐(Cr)和肌酸激酶同工酶(CK-MB),记录尿量及72 h生存率.结果 两组失血后2 h MAP均显著降低;随后VPA治疗组MAP(mm Hg,1 mm Hg=0.133 kPa)迅速回升,于失血后4、8和24 h显著高于相应休克对照组(58.4±7.6比40.3±5.0,84.4±8.0比56.4±4.4,92.6±10.3比72.6±8.9,P＜0.05或P＜0.01).VPA治疗组0～8、8～24、24～48和48～72 h尿量均显著多于休克对照组,但仍显著少于失血前(0 h).两组失血后血浆ALT、Cr和CK-MB均较0 h显著升高;VPA治疗组失血后4 h起器官功能指标显著低于休克对照组[ALT(U/L):80.1±9.8比112.2±10.1;Cr(μmol/L):74.5±8.3比88.0±7.6;CK-MB(kU/L):10.39±1.10比13.67±1.46,P＜0.05或P＜0.01],但失血后72 h仍显著高于0 h(ALT:79.5±7.1比40.5±4.4;Cr:85.6±7.1比46.6±4.8;CK-MB:7.63±0.86比1.66±0.21,均P＜0.01).VPA治疗组失血后72 h生存率显著高于休克对照组[70%(7/10)比20%(2/10),P＜0.05].结论 犬42%血容量失血后静注VPA能有效提高MAP,增加尿量,减轻器官功能损害,提高72 h早期生存率,有潜力成为战争或突发事故及灾害时低血容量休克现场救治的有效药物.     

脑卒中患者鞘内神经干细胞注射半年后功能状态评估

背景近年研究证实中枢神经组织有再生能力,但损伤后修复功能较差,很多实验结果不能令人满意.既往的脑移植或脑组织移植最大的生物学障碍是移植物难以在宿主体内生存或发育,移植效果的稳定性及其功能的恢复不肯定.目的探讨鞘内神经干细胞注射治疗脑卒中的方法,观察其疗效及副作用,以评价其安全性及可行性.设计以患者为研究对象,前后对照的验证性研究.单位一所市级医院神经内科和一所大学医院微生物与免疫学教研室.对象2002-11/2003-09安阳市人民医院神经内科住院脑卒中患者26例.其中3例为急性脑出血,其余23例病程3个月～30年,平均(4.2±6.6)年;男20例,女6例;年龄36～72岁,平均(56.3±12.7)岁;脑梗死15例,脑出血11例;合并高血压19例,冠心病2例,糖尿病4例,高脂血症4例.干预3例急性脑出血(出血量35～40 mL)患者行微创血肿穿刺术,通过引流管将细胞悬液注射到脑损伤处;其余病例均采用鞘内注射的方法将细胞悬液注入蛛网膜下腔,通过脑脊液循环至大脑表面.术后采用物理治疗、作业治疗及语言治疗进行康复.采用欧洲卒中量表评分标准(European stroke scale,SS)、生活功能评分标准(barthelindex,I)评价其疗效.ESS提高1分以上为有效,无提高或下降为无效.检查患者头颅CT,RI,心电图、胸部X射线片及血液生化学指标.主要观察指标疗效及副反应.结果23例行鞘内注射患者中,9例有效,例无效;移植后ESS评分54.1±21.2,较移植前51.4±21.1提高,差异有显著性意义(t=5.8,P=0.000 007 6);移植后BI 41.1±31.3,较移植前36.1±32.1提高,差异有显著性意义(t=7.11,=0.000 000 39).3例行微创血肿穿刺术急性脑出血患者均恢复良好,生活可基本自理.4例患者术后24 h内出现一过性发热,例患者术后感轻微头痛.结论研究表明神经干细胞移植后患者症状得到不同程度的缓解;且无明显毒副作用.证实神经干细胞移植用于改善脑卒中患者功能状态有效可行.