Risk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators

OBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors. DESIGN: Prospective cohort study. SETTING: The Cardiovascular Health Study (CHS). PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS. MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up. RESULTS: Among CHS participants (mean baseline age 73.3 years, 42% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 % CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease. CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.     

Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease

Recent investigations suggest that microthrombi formation in bowel capillaries could be a determinant factor in inflammatory bowel disease (IBD) pathogenesis. To evaluate the implication of the hemostatic system during these thrombotic events, we analyzed plasmatic values of prothrombotic state markers, physiologic inhibitors of coagulation, and endothelial lesion markers in 112 IBD patients. We found an increase in thrombin-antithrombin complexes and a decrease in antithrombin III, probably due to consumption, demonstrating an increase in thrombin generation. High levels ofd-dimer reflect increased fibrin formation, but there is no correlation between thrombin generation markers andd-dimer, possibly suggesting the presence of inadequate fibrinolysis. Levels of tissue factor pathway inhibitor were higher in patients than in controls. Nine patients with Crohn's disease (35% of our sample) had levels of this marker under 70% (range 37–69%). Von Willebrand factor values were increased and those of thrombomodulin only in active patients. Most of the changes were detected in patients with inflammatory activity, and there were no differences between ulcerative colitis and Crohn's disease. In conclusion, these results support the hypothesis that there is an endothelial lesion with sustained coagulation activation in IBD patients.     

贫困地区婴幼儿喂养健康教育路径效果评估

目的 研究在贫困地区有效推广科学喂养婴幼儿的理念和方法的路径效果, 改善喂养人的喂养技能, 达到提高婴幼儿健康水平的目的。方法 为完成国家“消除婴幼儿贫血行动”健康教育任务, 依托国家项目的政策、管理、技术平台, 采用临床路径及成人培训方法, 对基层业务人员及婴幼儿家长进行多轮培训;用婴幼儿喂养指数及喂养困难两个指标评价培训效果。结果 1)培训前后婴幼儿喂养指数各年龄组改善显著。培训前, 各年龄组均低于城市样本, 6~8个月龄低于农村样本, 9~11月龄与农村样本相似, 12~24月龄高于农村样本;培训后, 各年龄组均高于培训前的水平。2)培训前后喂养困难9~11月龄组改善不显著, 其余各年龄组改善显著。9~11月龄组喂养困难显示出涉及面宽、警示度低的特点, 依据是:问卷共14个项目, 该组有8个项目差异不显著;问卷每项最高分为7分, 该组干预前后分值分别为2.61±1.154、2.51±1.115。结论 临床路径的健康教育方法, 可全面、有效改善家长的婴幼儿喂养水平;但对于喂养困难, 需要更加系统和有针对性的措施。     

神经再生相关信号通路的研究进展

神经再生作为医学难题之一,其相关机制的研究不断深入,目前已达细胞分子水平。本文将近些年来与神经再生相关的信号通路研究作一综述,以期深入认识神经细胞对损伤的应答机制,为不同神经损伤的治疗提供积极的理论指导,并为发展新的治疗方法提供更多思路。     

The interaction between Toll-like receptor 4 signaling pathway and hypoxia-inducible factor 1α in lung ischemia–reperfusion injury

Background

Lung ischemia–reperfusion injury (LIRI) is the life-threatening complication occurring after lung transplantation. Toll-like receptor 4 (TLR4) signaling pathway and hypoxia-inducible factor-1α (HIF-1α) are intimately involved in the development and progression of various inflammatory and hypoxia diseases; however, the relationship of them in LIRI in vivo is still far from clear.

Materials and methods

Forty-five Sprague–Dawley rats were randomly distributed in nine groups: (1) Sham group, (2) LIRI group, (3) LIRI + saline control group, (4) LIRI + dimethyl Sulfoxide control group, (5) LIRI + lipopolysaccharide group, (6) LIRI + TAK-242 group (TAK-242 is a TLR4 inhibitor, ethyl (6R)-6- [N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate), (7) LIRI + thioredoxin group (thioredoxin is an apoptosis signal–regulating kinase 1 (ASK1) inhibitor), (8) LIRI + SB203580 group (SB203580 is a p38 inhibitor), and (9) LIRI + chetomin group (chetomin is a HIF-1α inhibitor). The interaction between TLR4 signaling pathway (including TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), ASK1, and p38) and HIF-1α and the role of TLR4-dependent HIF-1α were analyzed.

Results

In LIRI, HIF-1α accumulation was induced in a TLR4-dependent fashion, and MyD88, but not TRIF, and activation of ASK1 and p38 were found to be critical for TLR4-mediated HIF-1α accumulation. HIF-1α protein played a critical role in TLR4-mediated lung injury of LIRI (including inflammation, cell apoptosis, and lung damage). HIF-1α protein upregulated TLR4 expression of LIRI in a positive feedback manner.

Conclusions

We identify that the TLR4-HIF-1 loop may be existed in LIRI. Therefore, we suggest that the interaction between them may represent a novel therapeutic target for the development of novel target-based therapies of LIRI.     

The role of mRNA splicing in prostate cancer

Alternative splicing （AS） is a crucial step in gene expression. It is subject to intricate regulation, and its deregulation in cancer can lead to a wide array of neoplastic phenotypes. A large body of evidence implicates splice isoforms in most if not all hallmarks of cancer, including growth, apoptosis, invasion and metastasis, angiogenesis, and metabolism. AS has important clinical implications since it can be manipulated therapeutically to treat cancer and represents a mechanism of resistance to therapy. In prostate cancer （PCa） AS also plays a prominent role and this review will summarize the current knowledge of alternatively spliced genes with important functional consequences. We will highlight accumulating evidence on AS of the components of the two critical pathways in PCa： androgen receptor （AR） and phosphoinositide 3-kinase （PI3K）. These observations together with data on dysregulation of splice factors in PCa suggest that AR and PI3K pathways may be interconnected with previously unappreciated splicing regulatory networks. In addition, we will discuss several lines of evidence implicating splicing regulation in the development of the castration resistance.     

慢性硬膜下血肿临床路径对抗菌药物合理使用的作用

目的探讨慢性硬膜下血肿临床路径对抗菌药物合理使用的影响。方法选取2009年5月至2010年5月,实行临床路径管理之前按照传统医疗模式治疗慢性硬膜下血肿患者64例(对照组);2010年5月至2011年7月实行临床路径管理治疗的慢性硬膜下血肿患者60例(观察组),对照组依照经验预防使用抗菌药物治疗。观察组根据慢性硬膜下血肿的发生及发展的临床特点制定预防应用抗菌药物治疗方案并按照临床路径表开展医疗活动。观察两组患者的住院时间及抗生素的使用情况。结果观察组的住院时间为(8.46±2.67)d,明显低于对照组的(10.88±4.12)d;观察组和对照组的抗菌药物的使用率分别为68.33%、100%,观察组明显低于对照组;观察组抗菌药物的使用时间为(1.58±1.24)d,对照组为(7.64±1.52)d,观察组使用时间明显少于对照组;观察组的抗菌药物的费用是(247.82±89.62)元,相比于历史对照组的(2396.53±158.8)元明显降低,差异均有统计学意义(P0.05)。结论临床路径对于慢性硬膜下血肿的患者而言,在抗菌药物的使用方面具有较好的指导作用。有助于降低抗菌药物的使用率,规范使用时机、疗程,降低抗菌药物的总费用。     

急性脑梗死患者不同部位脑白质病变对认知功能的影响

目的 探讨急性脑梗死患者不同部位脑白质病变对认知功能的影响,分析胆碱能通路损伤部位与认知功能损害的关系.方法 选择急性脑梗死患者97例,以头颅MRIT2加权像评估是否有脑白质病变,其中有脑白质病变59例（脑白质病变组）,无脑白质病变38例（非脑白质病变组）.分别采用胆碱能通路高信号量表（CHIPS）及改良Scheltens量表对脑白质病变组进行评分.采用蒙特利尔评估量表（MoCA）对所有患者进行认知功能评分,观察两组认知功能差异,及CHIPS评分和改良Scheltens量表评分与MoCA评分的关系.结果 脑白质病变组与非脑白质病变组MoCA总分及视空间与执行、记忆、注意评分比较差异均有统计学意义[（20.86±4.52）分比（23.47±4.49）分、（3.80±1.68）分比（3.11±1.47）分、（2.78±1.57）分比（1.95±1.80）分、（4.00±2.08）分比（3.87±2.04）分]（P＜0.01或＜0.05）.有认知功能损害组（35例）与无认知功能损害组（24例）CHIPS评分和改良Scheltens量表评分比较差异均有统计学意义[（47.77±12.36）分比（39.83±7.98）分、（5.14±1.73）分比（2.58±2.10）分]（P＜0.01）.MoCA总分与额部脑室旁、枕部脑室旁、顶叶的脑白质病变评分及脑室旁总分、深部白质总分及改良Scheltens量表总分呈显著负相关（P＜0.01）.视空间与执行、注意、定向评分及MoCA总分与CHIPS评分呈负相关（P＜0.01）,注意、定向评分及MoCA总分与改良Scheltens量表评分呈负相关（P＜0.01）.结论 急性脑梗死患者脑白质病变与认知功能损害有关,且脑白质病变严重程度与认知功能损害程度有关;不同部位的脑白质病变对认知功能的影响不同;脑白质病变所致的认知功能损害与胆碱能通路受损有关,主要影响视空间及执行功能,其严重程度与胆碱能通路损害严重程度也有相关性.     

Notch信号通路在哮喘及T淋巴细胞调节中的作用研究进展

Notch信号通路参与多种组织细胞的分化、成熟过程,尤其在T 淋巴细胞的分化过程中起了决定性作用。近年来,大量研究表明,Notch 信号通路参与支气管哮喘（BA）发病的整个病理过程,包括气道炎症、气道高反应、气道重塑及气道血管重塑。笔者拟就 Notch 信号通路在 BA和 T淋巴细胞调节中的作用,进行综述如下。     

临床路径在无痛人工流产中的应用

目的：探讨临床路径在无痛人工流产中的应用价值及可行性。方法将440例行无痛人工流产患者分为临床路径组及非临床路径组（各为220例）,比较门诊无痛人工流产术临床路径组与非临床路径组在费用、患者就诊时间及满意度等方面的差别。结果与非临床路径组相比,无痛人工流产临床路径组费用明显下降（t＝30．05,P＜0．05）,就诊花费时间缩短（t＝8．61,P＜0．05）,满意度提高（χ^2＝6．05,P＜0．05）,人工流产并发症明显减少（χ^2＝6．05,P＜0．05）。结论门诊无痛人工流产可以实行临床路径管理,流程优化及降低费用效果明显,并发症明显减少。