α_2-肾上腺素能受体激动剂B-TH933抑制LPS处理的心肌细胞释放TNF-α

目的:观察α2-肾上腺素能受体激动剂B-HT933对脂多糖(LPS)刺激的心肌细胞产生肿瘤坏死因子α(TNF-α)的影响,并初步分析其作用机制。方法:分离培养SD大鼠乳鼠心肌细胞。利用免疫荧光染色观察心肌α2A-肾上腺素能受体的分布;B-HT933和/或LPS处理心肌细胞一定时间后,用ELISA方法检测细胞培养液中TNF-α的含量、实时荧光定量PCR测定心肌细胞TLR4和TNF-αmRNA的表达、Western blot分析心肌细胞中相关信号分子的磷酸化水平。结果:免疫荧光染色证实乳鼠心肌细胞中存在α2A-肾上腺素能受体。LPS以剂量和时间依赖的方式刺激心肌细胞产生TNF-α,0.1μmol/L的B-HT933处理能显著抑制LPS诱导的TNF-αmRNA的表达和TNF-α蛋白的产生。而且,BHT能抑制LPS诱导的心肌细胞IκBα的磷酸化。结论:乳鼠心肌细胞上存在α2A-肾上腺素能受体,其激动剂B-HT933可能通过抑制心肌细胞IκBα的磷酸化来减少LPS诱导的TNF-α产生。     

人脐带间充质干细胞移植治疗强直性脊柱炎

目的观察人脐带间充质干细胞移植治疗强直性脊柱炎的疗效。方法采用人脐带间充质干细胞治疗强直性脊柱炎病人10例,对干细胞移植治疗的患者分别在移植治疗前后的临床症状评分和化验检查进行监测。结果干细胞移植治疗后患者的BASDAI、夜间疼痛VAS和BASFI较治疗前均有明显下降;干细胞移植治疗后患者的血沉和免疫球蛋白G较治疗前有明显下降。结论脐带间充质干细胞移植治疗强直性脊柱炎安全有效。     

Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel

Mesoridazine, a phenothiazine antipsychotic agent, prolongs the QT interval of the cardiac electrocardiogram and is associated with Torsade de pointes-type arrhythmias. In this study, we examined the effects of mesoridazine on human ether-a-go-go-related gene (HERG) K+ currents. HERG channels were stably expressed in human embryonic kidney 293 cells and studied using standard whole-cell patch-clamp technique (37 degrees C). Mesoridazine blocked HERG currents in a concentration-dependent manner (IC50 550 nM at 0 mV); block increased significantly over the voltage range where HERG activates and saturated at voltages eliciting maximal HERG channel activation. Tonic block of HERG current by mesoridazine (1.8 microM) was minimal (< 2-4%). The rate of the onset of HERG channel block was rapid and dose dependent (tau = 54 +/- 7 ms at 0 mV and 1.8 microM mesoridazine), but not significantly affected by test potentials ranging from -30 to +30 mV. The V1/2 for steady-state activation was shifted from -31.2 +/- 1.0 to -39.2 +/- 0.5 mV (P < 0.01). The apparent rate of HERG channel deactivation was significantly reduced (fast tau = 153 +/- 8 vs. 102 +/- 6 ms at -50 mV, P < 0.01; slow tau = 1113 +/- 63 vs. 508 +/- 27 ms, P < 0.01). The inactivation kinetics and voltage dependence of steady-state inactivation of the HERG channel were not significantly altered by mesoridazine. These findings demonstrate that mesoridazine is a potent and rapid open-channel blocker of HERG channels. This block would explain the QT prolongation seen clinically at therapeutic concentrations (0.3-3.6 microM).     

低密度脂蛋白受体抑制剂对低密度脂蛋白和脂蛋白(a)代谢的影响

应用低密度脂蛋白受体抑制剂乳酸肝褐质和受体结合蛋白经刺猬腋下静脉注入，２ｍｉｎ后注射１２５Ⅰ－低密度脂蛋白或１２５Ⅰ－脂蛋白（３），６ｈ后处死，测定血、肝、肾、脾、胆汁和肾上腺的放射活性。实验发现：乳酸肝褐质和受体结合蛋白均能抑制低密度脂蛋白受体活性，使各组织摄取低密度脂蛋白分别降低１５％～８６％以上，但乳酸肝褐质和全体结合蛋白对脂蛋白（ａ）的组织摄取不但无抑制作用，反而能使脂蛋白（ａ）进入组织量增加，激活率分别达４０％～１２６％。实验结果说明：脂蛋白（ａ）虽然与低密度脂蛋白结构相似，含有７０％载脂蛋白Ｂ１００，但由于与载脂蛋白（ａ）以二硫键的形式连接，改变了空间结构，失去了与低密度脂蛋白受体结合的能力，并且推测乳酸肝褐质和受体结合蛋白在抑制低密度脂蛋白受体的同时，可能激活了细胞膜的其它机制，从而利于脂蛋白（ａ）进入细胞内。     

医务人员高暴露人群严重急性呼吸综合征隐性感染与工作强度和工种的相关性研究

目的　了解密切接触严重急性呼吸综合征 (SARS)患者的医护人员隐性感染的发生情况 ,及其与工作强度和工种之间的关系。方法　对北京中日友好医院密切接触SARS患者的 112 7名医务人员和 92名对照者的血清进行冠状病毒抗体 (IgG、IgM)酶联免疫吸附测定法 (ELISA)检测。并调查抗体阳性者周围密切接触者 313名的临床表现。结果　 112 7名SARS病区工作的医务人员 :男2 87名 ,女 84 0名 ;年龄 2 1～ 5 5岁 ,平均年龄 (34± 9)岁。对照组和医务人员上岗前所测冠状病毒抗体均为阴性 ,上岗后冠状病毒抗体阳性者共 2 9名 ,阳性率 2 5 7% (2 9/ 112 7)。特异性抗体的阳性率与工种和病区的关系结果提示 :抗体阳性的护士 2 1名 ,抗体阳性率占护士上岗人数的 3 4 6 % (2 1/ 6 0 7) ;医师、医技人员 6名 ,阳性率占其上岗人数的 1 4 1% (6 / 4 2 6 ) ;督导 2名 ,阳性率占其上岗人数的 2 86 %(2 / 70 )。ICU病区的 130名工作人员中抗体阳性者 10名 ,阳性率为 7 6 9% (10 / 130 ) ,占 2 9名抗体阳性者的 34 5 % (10 / 2 9) ;其他病区人员 19名 ,占 6 5 5 % (19/ 2 9)。 2 9名抗体阳性医务人员的周围密切接触者 313名 ,无一名发病或有临床症状。结论　密切接触SARS患者的医护人员有隐性感染的发生 ,隐性感染者从流行病学     

Gastrointestinal hormone abnormalities and G and D cells in functional dyspepsia patients with gastric dysmotility

AIM: To investigate the relationship between gastric dysmotility, gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD). METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT) were measured by radioimmunoassay in all the subjects. G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis. RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying. CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.     

Hemangiopoietin, a novel human growth factor for the primitive cells of both hematopoietic and endothelial cell lineages

The cells of hematopoietic and vascular endothelial cell lineages are believed to share a common precursor, termed hemangioblast. However, the existence of a growth factor acting relatively specifically on hemangioblasts remains unclear. Here we report the identification of hemangiopoietin (HAPO), a novel growth factor acting on both hematopoietic and endothelial cell lineages. In vitro in the human system, recombinant human HAPO (rhHAPO) significantly stimulated the proliferation and hematopoietic and/or endothelial differentiation of human bone marrow mononuclear cells and of purified CD34+, CD133+, kinase domain receptor-positive (KDR+), or CD34+/KDR+ cell populations. In the murine system, rhHAPO stimulated the proliferation of long-term culture-initiating cells (LTC-ICs) as well as CD34+ and stem cell antigen-1 (Sca-1+) cell subsets. In vivo, subcutaneous injection of rhHAPO into normal mice resulted in a significant increase in bone marrow hematopoietic cells. Furthermore, irradiated mice injected with rhHAPO had an enhanced survival rate and accelerated hematopoiesis. Our data suggest that HAPO is a novel growth factor acting on the primitive cells of both hematopoietic and endothelial cell lineages and that HAPO may have a clinical potential in the treatment of various cytopenias and radiation injury and in the expansion of hematopoietic and endothelial stem/progenitor cells.     

Insight into the efficient catalytic conversion of biomass to EG and 1,2-PG over W–Ni bimetallic catalyst

In this work, a mesoporous silica microsphere (MSM) was selected as a support to prepare a bimetallic supported catalyst (15% W–5% Ni/MSM) by a co-impregnation method that was simple and easy to conduct. We wished to improve the capability of catalytic conversion of biomass into ethylene glycol (EG) and 1,2-propylene glycol (1,2-PG). 15% W–5% Ni/MSM was examined on microcrystalline cellulose (cellulose) and corn stalks in a one-pot catalytic process, and total yields of EG and 1,2-PG reached up to 82.40 wt% and 62.60 wt%, respectively. This remarkable catalytic performance of W–Ni/MSM catalyst could be attributed to the synergistic effect between the active sites of Ni and W and the unique structure of MSM, which was suitable for mass transfer and metal loading. Based on physicochemical characterizations, the metal component was well-distributed on the surface of the MSM, and the metallic Ni, W and WO₃ of the fresh catalyst were converted mainly into NiWO₄ during the catalytic conversion of cellulose. To shed light on the reaction mechanism of the catalyzed hydrogenation of biomass, a possible process involving the formation of H_xWO₃ homogeneous catalysts, cellulose hydrolysis, C–C cleavage and hydrogenation conversion to 1,2-PG and EG was illustrated. Furthermore, the reusability of W–Ni/MSM catalyst was tested and we explored the cause of decreased diols yields. In summary, this work provides important guidance to rationally design effective catalysts for biomass conversion.

Bimetallic supported catalyst (W-Ni/MSM) was proposed to improve capability of catalytic conversion and investigated reaction pathway of lignocellulose into ethylene glycol and 1,2-propylene glycol.     

糖尿病心肌病影像诊断研究进展

糖尿病心肌病(diabetic cardiomyopathy,DCM)可导致糖尿病患者心力衰竭甚至死亡,是糖尿病的一种严重的并发症。早期表现为能量代谢、心肌脂肪变性、微循环灌注异常等,逐步发展为心肌细胞重塑、心功能异常和心肌纤维化等。DCM起病隐匿,致病分子机制尚未完全阐明,诊断标准不明确。目前可通过一些影像学检查间接检测心肌细胞可能存在的病理改变,做出诊断,及时干预,并监测病情发展,逆转或延缓病情,改善预后。本文就DCM病程中不同阶段的影像检测方法进行相关综述。