EL9611红白血病小鼠急性GVHD动物模型的建立

目的: 建立EL9611红白血病小鼠急性移植物抗宿主病(GVHD)的动物模型。方法: 同种异基因骨髓移植(allo-BMT)以C57BL/6(H-2^b)鼠为供鼠,BALB/c(H-2^d)为受鼠。设白血病组(n=10)、照射对照组(白血病鼠照射后不进行allo-BMT,n=4)、GVHD组(白血病鼠照射+allo-BMT,n=10)及正常对照组(n=4)。白血病组采用每只BALB/c鼠尾静脉输注2×10⁶个EL9611红白血病细胞建立红白血病动物模型;GVHD组于接种白血病细胞7 d后行总剂量为8.0 Gy的1次性 γ射线全身照射(TBI),照射后5 h内每只小鼠尾静脉输注C57BL/6鼠骨髓细胞2×10⁶个＋脾细胞1×10⁷个,建立EL9611红白血病小鼠的急性GVHD动物模型。观察小鼠体位、皮毛、大便等临床表现,病理检查肝脾、皮肤、小肠、外周血和骨髓,计算生存率。结果: 白血病组生存时间(14.5±2.1) d ,生存时间与GVHD组相比P<0.01,死亡率100％,无自发缓解,死亡时肝脾肿大(肝重2.40 g±0.48 g,脾重0.84 g±0.20 g,与正常对照组比P<0.01),外周血WBC升高 ,病理检查示组织正常结构破坏,白血病细胞浸润。照射对照组生存时间为(9.0±0.7) d,生存时间与GVHD组和正常对照组相比差异显著(P<0.01),死亡率100％,病理检查显示造血衰竭。GVHD组生存时间为(32.0±3.2)d,生存时间与其它各组相比P<0.01,死亡率100％,allo-BMT后第10-13 d出现症状,临床表现和病理检查符合Ⅰ到Ⅱ度GVHD的改变。结论: 采用EL9611红白血病细胞(2×10⁶/鼠)静脉输注的方式可成功建立EL9611红白血病动物模型;接种EL9611红白血病细胞第7 d行TBI +allo-BMT可成功建立EL9611红白血病小鼠的急性GVHD动物模型。     

内蒙古地区慢性粒细胞白血病患者HLA-DRB1基因多态性的研究

目的为研究内蒙地区汉族人群人类白细胞抗原（human leukocyte antigen,HLA）DRB1基因与CML白血病的相关性。方法采用Luminex流式技术-序列特异性寡核苷酸探针反向杂交（flow cytometry-sequence specific oligonucle-otide probe,FLOW-SSOP）方法对内蒙地区39例慢性粒细胞白血病chronic myeloid leukemia,CML）患者HLA-DRB1等位基因多态性进行分析,以北方地区健康群体资料作为正常对照。结果在HLA-DRB1等位基因中,CML白血病组中DRB1＊1001,＊16XX等位基因频率高于对照组（0.593%,0.603%,P〈0.05）。结论 DRB1＊1001,DRB1＊16XX等位基因与CML相关联,可能是易感基因。     

Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians

Background

The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.

Methods

Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.

Objectives

To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.

Results

Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.

Conclusion

Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

5-脂氧合酶激活蛋白抑制剂MK886对人食管癌细胞系增殖和凋亡的影响

目的 5-脂氧合酶活化蛋白（FLAP）抑制剂MK886对人食管癌细胞系（KYSE-150和TE-3）增殖和凋亡的影响及作用机制。方法用2.5、5、10、20、40和80μmol/L的MK886干预体外培养的KYSE-150和TE-3细胞;xCELLigence RTCA系统实时测定细胞增殖抑制率,同时确定半数抑制浓度(IC₅₀)。流式细胞测量术检测食管癌细胞的细胞周期。Western blot检测细胞凋亡和自噬相关蛋白的表达。结果人食管癌细胞系（KYSE-150和TE-3）的增殖抑制率随着MK886浓度增加而增强（P<0.05）,KYSE-150组的IC₅₀浓度为29.11μmol/L,TE-3组的IC₅₀浓度为27.47μmol/L。当MK886浓度增加至25μmol/L时,食管癌细胞G₀/G₁期滞后增加明显（P<0.001）,MK886处理浓度增加到50μmol/L时,食管癌细胞G₂/M期增加明显（P<0.001和P<0.05）...     

精神障碍患者自我面孔识别的行为特征与异常神经活动

自闭症、精神分裂症、抑郁障碍等精神障碍患者均表现出自我面孔识别缺陷。行为特征包括识别困难、错误率更高、反应速度更慢、速度加工优势消失、知觉加工受损及认知评价与情绪反应失调等;神经活动异常出现在自我面孔识别的各个加工阶段,涉及面孔结构编码相关的枕颞皮层、自我参照加工相关的皮质中线结构、认知控制有关的额顶控制网络以及情绪加工相关的脑岛等脑区。元分析结果揭示精神障碍患者额下回、内侧前额叶、海马旁回和脑岛等脑区活动存在异常。未来研究应结合时间和空间信息数据并关注脑区间协同功能的损伤,关注各类精神障碍患者自我面孔识别的共同特征及其独特性,并发掘自我面孔识别在精神障碍早期诊断中的潜在价值。     

Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach

Aims

We used propensity scores matching techniques to assess the association between maternal cocaine abuse in pregnancy and the occurrence of placenta-associated syndromes (PAS).

Study design

Mothers who abused cocaine (n = 5026) were matched to controls (n = 5026) from a sample of 1,693,197, unexposed mothers in Florida from 1998 to 2007. Cocaine abuse was identified using the ICD-9 principal and secondary diagnosis codes (304.2 for cocaine dependence and 305.6 for cocaine abuse). The outcome of interest, PAS, was identified as any indication in diagnosis field of ICD-9-CM codes for: placental abruption (641.2), oligohydramnios (658.0), placental infarction (656.7, 656.8, 656.9), gestational hypertension (642.3, 642.9), preeclampsia (642.4, 642.5, and 642.7) or eclampsia (642.6).

Results

Nearly 6% of mothers in the study sample experienced a condition associated with PAS prior to matching. Women who abused cocaine were 58% more likely to have PAS when compared to women who did not (OR = 1.48, 95% confidence interval: 1.33, 1.66). Women who abused cocaine were at elevated odds for placental abruption, placenta infarction and preeclampsia with the most pronounced odds noted for placental abruption (OR = 2.79, 95% confidence interval: 2.19, 3.55).

Conclusions

These findings indicate that cocaine abuse during pregnancy is associated with more placenta-related disorders than previously reported.     

《医院会计制度》修订应体现行业特点

随着公共财政体制各项政策的建立,医疗卫生体制改革的不断深入,对10年前制定的医院会计制度进行适时修订,能够满足推进公立医院改革和加强公立医院财务管理的需要。但《医院会计制度》的修订,不宜过度借鉴国际通行做法和企业会计制度经验,应体现我国医院行业的特点,才能指导会计核算工作,增加适应性和可操作性。