消化道肿瘤肝转移的介入治疗

介入治疗方法是一种微创手术,具有损伤小、近期疗效显著、并发症少、易于重复等特点,愈来愈得到国内外学者的重视.目前,肝动脉栓塞化疗、瘤内无水酒精注射等介入治疗已经得到了广泛应用,各种新技术不断应用于转移性肝癌介入治疗,并显示了较好的治疗效果.转移性肝癌的介入治疗方法多种,主要包括经皮的局部消蚀法和经血管的介入方法两大类.     

Diabetes in pregnancy outcomes: A systematic review and proposed codification of definitions

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies. Copyright © 2015 John Wiley & Sons, Ltd.     

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

Zebrafish with the young (yng) mutation show a defect in retinal cell differentiation. Here we demonstrate that a mutation in a brahma-related gene (brg1) is responsible for the yng phenotype. Brahma homologues function as essential subunits for SWI/SNF-type chromatin remodeling complexes. Our analysis indicates that brg1 is required for the wave of mitogen-activated protein kinase activity that precedes retinal cell differentiation. Using specific inhibitors of the mitogen-activated protein kinase pathway we show this signal has a direct role in retinal cell differentiation. Lastly, through investigations of mutants in other chromatin remodeling subunits, we provide genetic evidence for gene and tissue specificity of the Brahma chromatin remodeling complex.     

LEE阴性STEC分离株IHA基因的筛选、克隆及序列分析

尽管类志贺毒素对于STEC感染的临床及病理表现的产生非常重要,但细菌的一些毒性因子,特别是与肠道定居和粘附相关的因子也是病变产生的关键性决定因子。我们通过Southern杂交、克隆、打点杂交和序列测定等方法,获得了LEE阴性STEC O113:H7分离株98NK2染色体上大小为5.2kb的Hind III酶切片段的完全DNA序列,其中包含的一个大小为2088bp的开放阅读框架IhaO113(IrgA homologue adhesin)与LEE阳性STEC O157:H21分离株染色体上的一个假定粘附素IhaO157的核酸序列具有93%的一致性,两者的推导氨基酸序列具有91%的一致性。本研究首次报道了LEE阴性STEC O113:H7分离株染色体上预期与细菌粘附相关的编码基因Iha的完全DNA序列,为进一步研究其致病的分子机制提供了重要的理论依据。     

Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations

Aims/hypothesis Mutations at the gene encoding wolframin (WFS1) cause Wolfram syndrome, a rare neurological condition. Associations between single nucleotide polymorphisms (SNPs) at WFS1 and type 2 diabetes have recently been reported. Thus, our aim was to replicate those associations in a northern Swedish case–control study of type 2 diabetes. We also performed a meta-analysis of published and previously unpublished data from Sweden, Finland and France, to obtain updated summary effect estimates. Methods Four WFS1 SNPs (rs10010131, rs6446482, rs752854 and rs734312 [H611R]) were genotyped in a type 2 diabetes case–control study (n = 1,296/1,412) of Swedish adults. Logistic regression was used to assess the association between each WFS1 SNP and type 2 diabetes, following adjustment for age, sex and BMI. We then performed a meta-analysis of 11 studies of type 2 diabetes, comprising up to 14,139 patients and 16,109 controls, to obtain a summary effect estimate for the WFS1 variants. Results In the northern Swedish study, the minor allele at rs752854 was associated with reduced type 2 diabetes risk [odds ratio (OR) 0.85, 95% CI 0.75–0.96, p = 0.010]. Borderline statistical associations were observed for the remaining SNPs. The meta-analysis of the four independent replication studies for SNP rs10010131 and correlated variants showed evidence for statistical association (OR 0.87, 95% CI 0.82–0.93, p = 4.5 × 10⁻⁵). In an updated meta-analysis of all 11 studies, strong evidence of statistical association was also observed (OR 0.89, 95% CI 0.86–0.92; p = 4.9 × 10⁻¹¹). Conclusions/interpretation In this study of WFS1 variants and type 2 diabetes risk, we have replicated the previously reported associations between SNPs at this locus and the risk of type 2 diabetes. An erratum to this article can be found at     

Transfusion of donor peripheral blood buffy coat cells as effective treatment for relapsed acute leukemia after transplantation of allogeneic bone marrow or peripheral blood stem cells from the same donor

BACKGROUND: The transfusion of same-donor peripheral blood buffy coat (PBBC) cells to chronic myelocytic leukemia patients in relapse after bone marrow transplantation has been increasingly used as an effective antileukemic therapy. A graft-versus-leukemia effect mediated by immunocompetent donor T cells underlies its success. In acute leukemia, however, the effect of this adoptive cellular immunotherapy has not been established, and the results are generally poor. STUDY DESIGN AND METHODS: Five patients, three with acute lymphoblastic leukemia and two with acute myelocytic leukemia, who relapsed within 6 months after allogeneic marrow transplantation were enrolled in a nonrandomized pilot study to receive donor PBBC cell transfusions either before or after undergoing cytoreductive chemotherapy. ABO genotyping and polymerase chain reaction amplification of human tetrameric short tandem repeats DNA typing were used to test for marrow chimerism. RESULTS: Two acute lymphoblastic leukemia patients-both of whom underwent chemotherapy before PBBC cell transfusions, experienced a complete remission, and developed acute and then chronic, extensive graft-versus-host disease-have been leukemia-free for 9 and 7 months, respectively. Repeated molecular studies of their marrow as early as 2 weeks to 8 months after treatment confirmed that the marrow was of donor origin. The other three patients, who chose not to undergo chemotherapy before PBBC cell transfusions, failed to achieve remission and died 14, 16, and 30 days, respectively, after leukemia relapse. CONCLUSION: Adoptive cellular immunotherapy may be effective for acute lymphoblastic leukemia patients in relapse after bone marrow transplantation if chemotherapy is administered before PBBC cell transfusions are initiated.     

Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line

Previous studies have shown that the bcl-2 gene encodes a mitochondrial protein that contributes to neoplastic cell expansion primarily by promoting cell survival through interference with "programmed cell death" (PCD), also termed "apoptosis." Because many chemotherapeutic drugs are capable of initiating pathways leading to apoptosis, we determined whether deregulated bcl-2 expression could render cells resistant to several drugs commonly used in the treatment of non- Hodgkin's lymphomas, including dexamethasone (DEX), methotrexate (MTX), 1-beta-D-arabinofuranosyl-cytosine (Ara-C), etoposide (VP-16), vincristine (VC), cisplatin (CP), and hydroperoxycyclophosphamide (4- HC). For these experiments, we achieved high levels of p26-Bcl-2 protein production in a human pre-B-cell leukemia line 697 by stable infection with a recombinant bcl-2-containing retrovirus and then compared these cells with control virus-infected 697 cells. Control 697 cells were induced to undergo apoptosis by all drugs tested as defined by DNA degradation into oligonucleosomal-length fragments, cell shrinkage, and subsequent cell death. In contrast, 697 cells with elevated Bcl-2 protein levels exhibited strikingly prolonged cell survival and markedly reduced DNA fragmentation when cultured in the presence of these antineoplastic agents. Although high levels of Bcl-2 protein protected 697 cells from the acute cytotoxic effects of DEX and the other drugs tested, Bcl-2 did not prevent these drugs from suppressing the proliferation of 697 cells. However, when 697 cells were treated with DEX or MTX for 3 days, then washed and cultured in semisolid media without drugs, bcl-2-virus-infected cells gave rise to colonies at much higher frequencies than 697 cells stably infected with control virus. These results indicate that by protecting 697 leukemic cells from the acute cytotoxicity of DEX and some other chemotherapeutic drugs, high levels of p26-Bcl-2 can create the opportunity for re-initiation of cell growth when drugs are withdrawn. The findings may be relevant to clinical correlative studies of non- Hodgkin's lymphoma patients that have found an association between worse prognosis and bcl-2 gene rearrangements or t[14;18] translocations.     

Stem cell factor amplifies newborn and sickle erythropoiesis in liquid cultures

A two-phase liquid-culture system was used to substantially amplify and differentiate erythroblasts, starting with mononuclear cells from the blood of normal adults, newborn infants, and patients with sickle cell anemia. After the first 7 days (phase 1), in medium plus fetal bovine serum (FBS) alone, or in combination with stem cell factor (SCF) or conditioned medium (CM), the cell number was unchanged, and the cells all looked like lymphocytes. These cells were then diluted into medium with erythropoietin (Ep) alone, with Ep and either SCF or CM, or in methylcellulose with the same factors (phase 2). After 14 days in liquid phase 2 with SCF and Ep, the cell numbers increased an average of 30-fold in the sickle, 24-fold in the newborn, and 4-fold in the normal adult cultures; almost all the cells were erythroblasts and erythrocytes. SCF in phase 1 increased the number of late progenitors (CFU-E) assayed in methylcellulose, with the largest number in sickle, followed by newborn cultures and then adult cultures. We conclude that erythroid progenitor cells survive for at least 7 days without Ep (but with FBS). Progenitor cells are amplified, particularly with SCF. Later in culture, SCF with Ep increases the final number of differentiated erythroid cells. Both the early and the late effects of SCF are most effective in sickle, followed by newborn cultures and then adult cultures.