胆囊切除术后腹泻的研究进展

胆囊切除术后腹泻(PCD)是胆囊切除术后综合征(PCS)的常见症状之一,不仅发病率高,且严重影响患者的工作和生活。因此,PCD的治疗已逐渐成为研究热点。然而,目前PCD的发病机制及其治疗方法尚不明确。本文就PCD的相关流行病学、病理生理、发病机制及治疗策略等方面进行综述。     

Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

脂质体介导Bcl-2反义寡核苷酸对胆管癌细胞株QBC939的作用

目的：观察Bcl-2反义硫代磷酸寡脱氧核苷酸（ASODN）对人胆管癌QBC939细胞的作用及对Bcl-2蛋白表达的影响。方法：脂质体LipofectamineTM2000介导Bcl-2 ASODN转染QBC939细胞,应用台盼篮拒染实验检测细胞存活率、克隆形成实验检测克隆形成率、Western blot检测Bcl-2蛋白表达。结果：Bcl-2 ASODN转染后Bcl-2蛋白免疫印迹条带光密度显著低于对照组（P<0.01）;台盼篮拒染实验和克隆形成实验均显示Bcl-2 ASODN可以部分抑制QBC939细胞增殖,经ASODN作用,细胞的存活率和克隆形成率均显著低于对照组（P<0.05）。结论：Bcl-2 ASODN通过封闭人胆管癌QBC939细胞bcl-2基因表达抑制人胆管癌QBC939细胞的增殖。     

海南虎刺枝叶中化学成分及其抗类风湿性关节炎活性研究

目的 研究茜草科虎刺属植物海南虎刺Damnacanthus hainanensis枝叶中的化学成分及其抗类风湿性关节炎活性。方法 综合运用硅胶柱色谱、反相硅胶柱色谱、Sephadex LH-20凝胶柱色谱以及制备型HPLC等色谱技术进行系统分离和纯化,根据分离得到化合物的理化性质及其波谱数据,并通过与文献中报道的波谱数据进行比对,鉴定化合物的结构;采用MTS法通过对分离得到化合物的体外抑制滑膜细胞增殖的活性进行测试以评价其抗类风湿性关节炎活性。结果 从海南虎刺枝叶的甲醇提取物中分离得到了18个化合物,分别鉴定为naucleidinal（1）、1,2,3,4-tetrahydronorharman-1-one（2）、19-O-methyl-3,14-dihydroangustoline（3）、latifoliamide B（4）、latifoliamide D（5）、bacilsubteramide A（6）、vinmajine I（7）、naucleofficine D（8）、1-甲氧甲酰-β-咔巴啉（9）、naphthisoxazol A（10）、1,6-dihydroxy-2-methyl-9,10-anthraquinone（11）、rubiadin-1-methyl ether（12）、1,3,6-trihydroxy-2-methoxymethyl-9,10-anthraquinone（13）、3,6-dihydroxy-2-hydroxymethyl-9,10-anthra quinone（14）、7-羟基色原酮（15）、5,7-二羟基色原酮（16）、6,4''-dihydroxy-3''-methoxyaurone（17）和farnisin（18）。抗类风湿性关节炎活性评价结果表明,化合物11～14、17和18对滑膜成纤维MH7A细胞增殖抑制活性的半数抑制浓度（median inhibition concentration,IC₅₀）值为（8.93±0.09）～（152.58±0.32）μmol/L。结论 所有化合物均为首次从虎刺属植物中分离得到。化合物11～14、17和18表现出了较为显著的抗类风湿性关节炎活性。     

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use,health-related quality of life,safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome

Objective: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP.

Methods: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1?mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS).

Results: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p?=?.0181) or for IBS-D (p?=?.0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported.

Conclusions: Alosetron 1?mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Reappraisal of the characteristics of glucose abnormalities in patients with chronic hepatitis C infection

OBJECTIVES: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection.
METHODS: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results.
RESULTS: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70–4.56, P < 0.001).
CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.