国内六大行政区域六城市中老年人群膝关节骨性关节炎患病危险因素比较

目的：了解中国不同地区间中老年人群膝关节骨性关节炎患病危险因素。方法：调查时间为2005—07／08。①从中国六大行政区（西北，华北，华东。中南，东北，西南）选出六城市（西安，石家庄，上海。广州，哈尔滨市，成都），用分层多阶段整群抽样方法，抽取6218名40岁及以上具有正式户口常住男女人群进行膝关节骨性关节炎的流行病学问卷调查（包括一般情况、现病史、既往史、体格检查、X射线片检查情况和疾病诊断6个方面，共计94个问题141个变量指标），并对其中4808名有症状者进行X射线平片膝正侧位投照。②膝关节骨性关节炎诊断标准为临床症状阳性加X射线Kellgren ＆ Lawrence分级二级及以上者。③计算患病率，并采用Epilnf06．0和SPSS 10．0软件对其中83个变量进行多因素非条件Logistfc回归分析，表示疾病与暴露因素之间联系强度的指标用比值比（OR），若OR〉1，说明疾病发生危险性增加，与暴露因素呈正关联；若OR〈1，说明疾病发生危险性减少，与暴露因素呈负关联。 结果：①六城市膝关节骨性关节炎总患病率为15．6％，其中西安7．7％，石家庄11．2％，上海9．8％。广州30．5％，哈尔滨16．9％，成都17．5％，各城市患病率比较差异显著（P〈0．01）。②Logistic回归分析膝关节骨性关节炎在大部分城市有共同的危险因素如年龄大（OR=1．032—1．181），使用蹲坑排便年限长（OR=1．021-1．077），体质量高（OR=1．048—1．073），和开始饮酒年龄大（OR=1．008～1．028）；而从事专职体育运动（OR=1．651，西安），骨质疏松病史（OR=3．311，石家庄），吸烟（OR=2．654，石家庄），类风湿关节炎病史（OR=4．964，上海），文化程度高（OR=2．593，上海），女性（OR=2．510，广州），姐妹骨关节炎史（OR=13．251，哈尔滨），母亲骨关节炎史（OR=5．683，成都）等危险因素分别在不同地区出现． 结论：年龄大、使用蹲坑排便年限长、体质量高和开始饮酒年龄大是中国六地区膝关节骨性关节炎患病的共同危险因素，同时，不同地区主要危险因素又有一定差异。     

经冠状动脉自体骨髓单个核细胞移植对扩张型心肌病兔心肌组织病理学的影响

目的:骨髓干细胞在扩张型心肌病动物模型中具有向心肌样细胞和血管内皮细胞分化的潜能。评价经冠脉自体骨髓单个核细胞移植治疗对扩张型心肌病兔心肌组织病理学影响及心功能的变化。方法:实验于2006-09/2007-03在复旦大学附属华山医院心血管研究室完成。①实验材料:3月龄雄性新西兰兔25只,随机数字表法分为正常组5只、模型组10只、冠脉移植组10只。②实验方法:冠脉移植组、模型组兔经耳缘静脉注射盐酸阿霉素建立扩张型心肌病模型。冠脉移植组10只兔麻醉后以髂骨为穿刺点,共采集15mL混有肝素生理盐水的骨髓液,密度梯度离心得到自体骨髓单个核细胞悬液2mL,其中5只兔的骨髓单个核细胞悬液行DAPI标记,经塑性的4F造影导管,模拟临床冠脉内输注细胞悬液。③实验评估:术后4周通过检测血流动力学指标评价心功能的改变;苏木精-伊红、天狼猩红染色观察心肌组织形态学特点,透射电镜观察心肌组织超微结构的改变;TnT间接免疫荧光检测心肌组织DAPI标记情况,以评价骨髓单个核细胞的分化和转归。结果:①血流动力学指标的测定:与基础值比较,细胞移植4周后模型组兔血流动力学指标无明显改变(P>0.05),而冠脉移植组心功能显著改善(P<0.05)。②心肌组织形态学观察:扩张型心肌病兔心肌纤维排列紊乱,坏死区大量淋巴细胞浸润,细胞间隙增宽,心肌间质面积增大。③心肌组织超微结构的变化:造模结束后,模型组心肌细胞线粒体肿胀,肌丝断裂,心肌细胞核呈锯齿状,心肌间质中淋巴细胞浸润,胶原纤维增多。细胞移植4周后,冠脉移植组出现线粒体堆积现象,亦存在巨噬细胞浸润和胶原纤维轻度增生,未发现心肌组织中存在植入的特殊类型细胞。④心肌组织TnT间接免疫荧光检测:DAPI标记的骨髓单个核细胞在心肌组织中富集,血管腔内不存在。结论:①经冠脉自体骨髓单个核细胞移植治疗阿霉素扩张型心肌病兔,利于植入细胞在心肌组织中富集,改善心功能。②透射电镜尚无法证实心肌组织中存在外来的移植细胞。     

Effect of known history of heart disease on survival outcomes after out‐of‐hospital cardiac arrests

Objective

We aimed to investigate the effect of known heart disease on post‐out‐of‐hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival.

Methods

This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009–2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non‐traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge.

Results

Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03–1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58–1.00). Other factors influencing survival corresponded with previous reports.

Conclusions

Known heart disease independently predicted poorer post‐OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.     

Mouse models in liver cancer research： A review of current literature

Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma （HCC）, as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.     

Asthma and chronic obstructive pulmonary disease: common genes, common environments?

Asthma and chronic obstructive pulmonary disease (COPD) show similarities and substantial differences. The Dutch hypothesis stipulated that asthma and COPD have common genetic and environmental risk factors (allergens, infections, smoking), which ultimately lead to clinical disease depending on the timing and type of environmental exposures (Postma and Boezen, Chest 2004;126:96S-104S). Thus, a particular group of shared genetic factors may lead to asthma when combined with specific environmental factors that are met at a certain stage in life, whereas combination with other environmental factors, or similar environmental factors at a different stage in life, will lead toward COPD. Multiple genes have been found for asthma and COPD. In addition to genes unique to these diseases, some shared genetic risk factors exist. Moreover, there are both common host risk factors and environmental risk factors for asthma and COPD. Here we put forward, based on the data available, that genes that affect lung development in utero and lung growth in early childhood in interaction with environmental detrimental stimuli, such as smoking and air pollution, are contributing to asthma in childhood and the ultimate development of COPD. Additional genes and environmental factors then drive specific immunological mechanisms underlying asthma, and others may contribute to the ultimate development of specific subtypes of COPD (i.e., airway disease with mucous hypersecretion, small airway disease, and emphysema). The genetic predisposition to the derailment of certain pathways may further help to define subgroups of asthma and COPD. In the end this may lead to stratification of patients by their genetic make-up and open new therapeutic prospects.     

Coronary-cameral fistulas in adults(first of two parts)

This is a case series and review of the literature adding11 new cases.Coronary-cameral fistulas(CCFs)are infrequent anomalies which are in general co-incidentally found during diagnostic coronary angiography(CAG).To delineate the characteristics of congenital and acquired CCFs in adults,we performed a PubMed search for papers dealing with congenital or acquired CCFs in adults.Publications on coronary-vascular fistulas or paediatric subjects were not included.From the world literature,a total of 243 adult patients were identified who had congenital(65%)or acquired(35%)CCFs.In this review,which is part one of a two-part series on CCFs,we describe and discuss the congenital fistulas,give an overview on the published literature and report details of our own series of 11 patients with MMFs and solitary macro CCFs.Of the congenital group,56%were small or large solitary macro CCFs(cut-off 1.5mm)and 9%were coronary artery-ventricular multiple micro-fistulas(MMFs).Apical hypertrophic cardiomyopathy was reported in some of the reviewed subjects with MMFs(3/24=13%)but not was seen in our own series.Conservative medical management was generally the treatment of choice in congenital MMFs;prophylactic implantable cardioverter defibrillators(ICD)were implanted in 2/24(8%)of subjects,especially when extensive micro-fistulisations were involved.None of the patients of our own series required an ICD,as the MMFs were of limited size.Congenital or acquired CCFs in adults are infrequent anomalies having a wide spectrum of clinical presentation may varies from asymptomatic to severely devastating states requiring different treatment modalities.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

The value of flow cytometric analysis of platelet glycoprotein expression of CD34+ cells measured under conditions that prevent P- selectin-mediated binding of platelets

In the present study, we show by adhesion assays and ultrastructural studies that platelets can bind to CD34+ cells from human blood and bone marrow and that this interaction interferes with the accurate detection of endogenously expressed platelet glycoproteins (GPs). The interaction between these cells was found to be reversible, dependent on divalent cations, and mediated by P-selectin. Enzymatic characterization showed the involvement of sialic acid residues, protein(s). The demonstration of mRNA for the P-selectin glycoprotein ligand 1 (PSGL-1) in the CD34+ cells by polymerase chain reaction (PCR) analysis suggests that this molecule is present in these cells. Under conditions that prevent platelet adhesion, a small but distinct subpopulation of CD34+ cells diffusely expressed the platelet GPIIb/IIIa complex. These cells were visualized by immunochemical studies. Furthermore, synthesis of mRNA for GPIIb and GPIIIa by CD34+ cells was shown using PCR analysis. The semiquantitative PCR results show relatively higher amounts of GPIIb mRNA than of PF4 mRNA in CD34+CD41+ cells in comparison with this ratio in platelets. This finding is a strong indication that the PCR results are not caused by contaminating adhering platelets. MoAbs against GPIa GPIb alpha, GPV, P- selectin, and the alpha-chain of the vitronectin receptor did not react with CD34+ cells. The number of CD34+ cells expressing GPIIb/IIIa present in peripheral blood stem cell (PBSC) transplants was determined and was correlated with platelet recovery after intensive chemotherapy in 27 patients. The number of CD34+CD41+ cells correlated significantly better with the time of platelet recovery after PBSC transplantation (r = .83, P = .04) than did the total number of CD34+ cells (r = .55). Statistical analysis produced a threshold value for rapid platelet recovery of 0.34 x 10(6) CD34+CD41+ cells/kg. This study suggests that if performed in the presence of EDTA the flow cytometric measurement of GPIIb/IIIa on CD34+ cells provides the most accurate indication of the platelet reconstitutive capacity of the PBSC transplant.     

Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.