Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Pick’s disease with Pick bodies combined with progressive supranuclear palsy without tuft‐shaped astrocytes: A clinical,neuroradiologic and pathological study of an autopsied case

We report clinical, neuroradiologic features, and neuropathologic findings of a 76‐year‐old man with coexistent Pick’s disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed‐ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau‐ and ubiquitin‐positive in neurons of layers II–III of the above‐mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau‐positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned‐astrocytes and coiled bodies but no‐tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick’s disease and coexistence with progressive supranuclear palsy without tuft‐shaped astrocytes.     

颅内肿瘤切除术后颅内感染危险因素分析

目的 探讨颅内肿瘤切除术后颅内感染的危险因素和预防措施。方法 回顾性分析442例颅内肿瘤切除术患者的临床资料。结果 442例颅内肿瘤切除术患者发生颅内感染33例，感染率为7．47％。非脑膜瘤手术颅内感染率为10．04％，高于脑膜瘤术后颅内感染率3．83％（P〈0．05）；手术时间≥4h者颅内感染率为9．87％，高于手术时间〈4h者颅内感染率4．78％（P〈0．05）；有脑脊液漏者颅内感染率为15．00％，高于无脑脊液漏者颅内感染率6．28％（P〈0．05）；引流管留置≥24h者颅内感染率为11．58％，高于未留置或留置〈24h者颅内感染率5．03％（P〈0．05）。结论 手术时间≥4h、引流管留置时间≥24h、存在脑脊液漏是颅内肿瘤切除术后发生颅内感染的危险因素。     

隐身南新仓的低调奢华

置身RAIN CLUB的超凡境地中，美食、美酒和美妙的音乐是智灵的洗净，像干燥的北京城迎来第一场春天的“润”——稍显奢华。[编者按]     

曲尼司特对豚鼠肺组织β肾上腺素受体向下调节的影响

用放射配体结合分析法分别测定了正常组、特布他林组、特布他林十曲尼司特组豚鼠的肺组织β受体最大结合力和解离常数,结果显示:给特布他林后豚鼠肺组织β受体发生明显的向下调节.曲尼司特可预防此向下调节的发生.     

Human osteoblasts' proliferative responses to strain and 17beta-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I.

The mechanism by which mechanical strain and estrogen stimulate bone cell proliferation was investigated using monolayer cultures of human osteoblastic TE85 cells and female human primary (first-passage) osteoblasts (fHOBs). Both cell types showed small but statistically significant dose-dependent increases in [3H]thymidine incorporation in response to 17beta-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17beta-estradiol occurred at 10(-8) - 10(-7) M and the peak response to strain occurred at 3500 microstrain ((mu)epsilon). Both strain-related and 17beta-estradiol-related increases in [3H]thymidine incorporation were abolished by the estrogen receptor (ER) modulator ICI 182,780 (10-8 M). Tamoxifen (10(-9) - 10(-8) M) increased [3H]thymidine incorporation in both cell types but had no effect on their response to strain. In TE85 cells, tamoxifen reduced the increase in [3H]thymidine incorporation associated with 17beta-estradiol to that of tamoxifen alone but had no such effect in fHOBs. In TE85 cells, strain increased medium concentrations of insulin-like growth factor (IGF) II but not IGF-I, whereas 17beta-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 microg/ml) blocked the effects of 17beta-estradiol and exogenous truncated IGF-I (tIGF-I; 50 ng/ml) but not those of strain or tIGF-II (50 ng/ml). Neutralizing antibody to IGF-II (3 microg/ml) blocked the effects of strain and tIGF-II but not those of 17beta-estradiol or tIGF-I. MAb aIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17beta-estradiol, and tIGF-I. HOBs and TE85 cells, act similarly to rat primary osteoblasts and ROS 17/2.8 cells in their dose-related proliferative responses to strain and 17beta-estradiol, both of which can be blocked by the ER modulator ICI 182,780. In TE85 cells (as in rat primaries and ROS 17/2.8 cells), the response to 17beta-estradiol is mediated by IGF-I, and the response to strain is mediated by IGF-II. Human cells differ from rat cells in that tamoxifen does not block their response to strain and reduces the response to 17beta-estradiol in TE85s but not primaries. In both human cell types (unlike rat cells) the effects of strain and IGF-II as well as estradiol and IGF-I can be blocked at the IGF-I receptor.     

眼针治疗阵发性室上性心动过速120例的即时疗效观察

目的:观察眼针对阵发性室上性心动过速的即时疗效。方法:选择符合诊断标准的门诊患者120例,针其眼针穴区:心区和上焦区。针后30分钟描记心电图,计算心率,观察眼针对阵发性室上性心动过速的影响。结果:显效103例,占85.83%;有效9例,占7.5%;无效8例,占6.66%;总有效率93.33%.结论:眼针对阵发性室上性心动过速有较好的即时疗效。     

肝细胞癌的相关血清标志物

HCC的早期诊断是其治疗的关键，HCC血清标志物的检测又为其诊断提供了有利的途径，并且操作简单，敏感性高和特异性强。目前常用的血清标志物为AFP、AFP变异体、AFP mRNA、AFU、GGT、DCP、AIF、GPC3等。这些标志物的联合使用有助于HCC的诊断及预后。     

手术治疗125例分化性甲状腺癌的5年随访结果分析

目的：探讨甲状腺全切除术在治疗分化性甲状腺癌中的临床应用价值。方法：采用我院1988年1月～2001年5月甲状腺全切除术或甲状腺侧叶切除加峡部切除术治疗分化性甲状腺癌125例,对其手术并发症发生、局部复发、转移情况及术后5年生存率进行回顾性对比分析。结果：甲状腺全切除术术后并发症发生率高于甲状腺侧叶切除加峡部切除术组;局部复发、转移率低于侧叶切除加峡部切除术组;5年生存率两组无显著性差异。结论：甲状腺全切除术是治疗甲状腺癌有效的手术方式,但应掌握手术指征,改进、提高手术技术,减少并发症。     

氟尿嘧啶化放疗的现状与未来

20世纪60年代在肿瘤的根治和辅助治疗中就使用了氟尿嘧啶（Fluorouracil，FU）化放疗（外放疗同时进行化疗）。2002年．全世界约200万肿瘤患者接受了FU治疗．其中很大一部分是以FU为基础的化放疗。FU是许多肿瘤患者的基础治疗药物。总之，FU化放疗显著改善了肿瘤的局部控制．并提高了部分肿瘤患者的生存率：也提高了部分具有重要功能的器官的保留。