肺血栓栓塞患者DNA氧化损伤的研究

目的探讨急性期及病情缓解后肺血栓栓塞（PE）患者氧化应激状态、外周血单个核细胞（PBMcs）DNA氧化损伤情况。方法采用单细胞凝胶电泳法（彗星试验）检测35例急性PE患者（试验组）及33例健康体检者（对照组）PBMCsDNA损伤程度;菲罗啉比色法检测血浆总抗氧化能力（TAC）;硫代巴比妥酸比色法检测血浆丙二醛（MDA）含量;改良Hafeman直接测定法（DNTB）检测血浆谷胱甘肽过氧化物酶（GSH—PX）活力。结果试验组病情缓解后血浆TAC、GSH．PX活性均较急性期明显升高[（6．86±1．21）kU／L比（5．18±1．13）kU／L、（165．25±41．96）kU／L比（137．23±38．52）kU／L],但均显著低于对照组[（7．85±1．44）,（189．92±51．32）kU／L],差异有统计学意义（P〈0．01）;试验组病情缓解后血浆MDA含量较急性期明显降低[（5．58±1．89）μmol／L比（7．26±2．25）μmol／L],但均显著高于对照组[（3．71±1．52）μmol／L],差异有统计学意义（P〈0．01）。试验组病情缓解后PBMCsDNA损伤程度（29．01±6．75）较急性期（42．13±8．01）明显减轻,但均显著高于对照组（15．12±4．36）,差异有统计学意义（P〈0．01）。试验组病情缓解后及急性期PBMCsDNA损伤均与血浆TAC呈负相关（r=-0．695,P〈0．01;r=-0．536,P〈0．01）、与血浆MDA含量呈正相关（r=0．513,P〈0．01;r=0．628,P〈0．01）;试验组病情缓解后及急性期血浆TAC均与MDA含量呈负相关（r=-0．534,P〈0．01;r=-0．486,P〈0．05）、与GSH．PX活性呈正相关（r=0．512,P〈0．01;r=0．497,P〈0．01）。结论PE患者急性期体内氧化／抗氧化失衡,存在氧化应激及其介导的PBMCsDNA损伤;PE患者病情缓解后,氧化应激及其介导的PBMCsDNA损伤减轻。     

急性冠状动脉综合征患者外周血血管性血友病因子水平与冠状动脉病变程度的相关性研究

目的 探讨急性冠状动脉综合征（ACS）患者外周血血管性血友病因子（vWF）水平与冠状动脉病变程度的相关性.方法 选取行冠状动脉造影148例ACS患者为ACS组.按ACS患者冠状动脉造影结果,所示病变累及相关冠状动脉支数分为单支病变组（54例）、双支病变组（51例）及多支病变组（43例）;并根据Gensini积分分为三组：Gensini积分≤20分31例（轻度组）,Gensini积分21～40分47例（中度组）,Gensini积分≥41分70例（重度组）.选取稳定型心绞痛（SA）患者50例为SA组,并选取50例冠状动脉正常者为对照组.检测外周血vWF水平,同时检测血常规、凝血功能、肝肾功能、超敏C反应蛋白（hs-CRP）、血糖、血脂等,并分析外周血vWF水平与冠状动脉病变程度的相关性.结果 ACS组白细胞计数和hs-CRP水平显著高于SA组及对照组,差异有统计学意义（P＜0.05）,但SA组与对照组比较差异无统计学意义（P＞0.05）;三组血小板计数、凝血酶原时间、活化部分凝血酶原时间、空腹血糖、凝血酶时间、餐后2h血糖、三酰甘油、总胆固醇比较差异无统计学意义（P＞0.05）.ACS组外周血vWF水平为（143.25±20.42）％,明显高于SA组和对照组的（102.77±11.84）％,（97.63±10.31）％,差异有统计学意义（P＜0.05）.单支病变组外周血vWF水平为（127.34±9.35）％,双支病变组为（144.81±12.02）％,多支病变组为（159.55土18.62）％,单支病变组、双支病变组、多支病变组、对照组组间比较差异有统计学意义（P＜0.01）;轻度组外周血vWF水平为（124.77土14.31）％,中度组为（132.53±16.38）％,重度组为（155.06±18.53）％,轻度组、中度组、重度组及对照组比较差异有统计学意义（P＜0.01）.ACS患者外周血vWF水平与冠状动脉病变支数和冠状动脉造影Gensini积分呈正相关（r=0.698,0.683,P＜0.01）.结论 ACS患者外周血vWF水平与冠状动脉病变严重程度关系密切,在评价ACS患者病情及指导治疗方面有重要临床意义.     

A novel individualized substrate modification approach for the treatment of long-standing persistent atrial fibrillation: Preliminary results

Background

The most effective approach for long-standing persistent atrial fibrillation (LPAF) ablation remained undetermined. Our goal was to explore the heterogeneous left atrial substrate in patients with LPAF and to evaluate the effectiveness of a novel individualized substrate modification (ISM) approach in LPAF ablation.

Methods

One hundred and twenty-four patients with LPAF were randomized to ISM group (n = 64) or stepwise ablation (SA) group (n = 60). After pulmonary vein isolation, ISM was performed in the ISM group and SA was applied in the SA group. The clinical effectiveness after a single and a repeated procedure was compared.

Results

The total procedural time was significantly shorter in ISM than that in SA. In the ISM group, mild left atrial substrate was observed in 17 (27.4%), moderate in 26 (41.9%) and severe in 19 (30.6%) patients after successful cardioversion of the 62 patients. The intention-to-treat analysis showed that sinus rhythm was maintained in 65.5% of patients in the ISM group and in 45.0% of patients in the SA group after a single procedure, P = 0.04. Atrial tachycardia (AT) recurred in 5 of 22 in the ISM group and in 20 of 33 in the SA group, P = 0.01. After a repeated procedure, 75% of patients in the ISM group and 63.3% of patients in the SA group were free of further recurrence, P = 0.16.

Conclusions

Left atrial substrate varied noticeably in patients with LPAF. The ISM approach was superior to SA approach in terms of procedural time, recurrence rate of AT and clinical effectiveness after a single procedure. However, they yielded comparable outcomes after a repeated procedure.     

The mechanism of damage by trace amounts of acetamiprid to the midgut of the silkworm,Bombyx mori

Acetamiprid is widely used for agricultural pest control. However, it remains poorly understood whether the environmental residues of acetamiprid have the potential effects on economic insect. In this study, we evaluated the effects of acetamiprid on silkworm growth and development. The exposure to trace amounts of acetamiprid significantly decreased body weight, viability, and spinning ability. In addition, the activity of trypsin in the midgut was decreased after exposure. DGE and KEGG pathway enrichment analysis revealed that the significantly differentially expressed genes were mainly involved in nutrient metabolism, stress responses, and inflammation pathways. These results, in combination with hematoxylin‐eosin staining and transmission electron microscopy, indicated that acetamiprid could cause oxidative damage to midgut, lead to inflammatory responses, and affect the activities of midgut digestive enzymes, thus resulting in abnormal growth and development. Our findings greatly contributed to the evaluation of the effects of acetamiprid residues on other nontarget beneficial insect.     

Serum biomarkers and the prognosis of AMI patients

Background

It has been proven that serum lactate dehydrogenase (LDH) and total bilirubin (TB) increase during acute myocardial infarction (AMI). However, how they influence the prognosis of AMI patients is still not completely known.

Methods

A total of 239 patients diagnosed with AMI and admitted to the Fourth Clinical Hospital of Harbin Medical University, between 2007 and 2008, were enrolled in this study. All the patients had not undergone primary percutaneous coronary intervention (PCI) because the time window (24 h) was missed. They all underwent PCI 1 week after the onset of symptoms. Serum high-sensitivity C-reactive protein (hs-CRP), TB, LDH, and other biomarkers were determined between 24 and 48 h of symptom onset. All of the patients were followed up for an average of 3.2±0.4 years for occurrence of major adverse cardiac events (MACE).

Results

Patients with MACE had significantly higher levels of hs-CRP, LDH, cystatin C, uric acid, a higher ratio of LDH and TB (LDH/TB), and a lower level of TB: 8.48±3.84 vs. 2.13±1.32 μmol/l, p<0.01; 1,355.8±654.3 vs. 1,151.7±415.4 U/l, p<0.01; 1.69±0.76 vs. 1.00±0.46 mg/l, p<0.01; 419.6±109.2 vs. 343.2±108.2 μmol/l, p<0.01 and 141.1±46.2 vs. 61.2±26.5, p<0.01; 18.3±6.7 vs. 14.8±6.6 mg/l, p<0.01, respectively. In the multivariate COX analysis, LDH, cystatin C, and LDH/TB were significantly associated with the prognosis of these patients.

Conclusions

Patients under higher oxidative stress tend to have more MACE. LDH, cystatin C, and LDH/TB are strongly related to the prognosis of AMI patients undergoing elective PCI.     

酒精性肝病与氧化应激

酒精性肝病(ALD)是威胁人类健康的重大疾病之一,其发病机制错综复杂。氧化应激性肝损害在其中占有至关重要的地位,如何系统的认识机体的氧化与抗氧化系统在ALD发生发展过程中所扮演的角色,对ALD的防治工作具有一定的指导意义。     

The Wee1 kinase inhibitor MK1775 suppresses cell growth,attenuates stemness and synergises with bortezomib in multiple myeloma

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138⁺ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138⁺ cells by decreasing ALDH1⁺ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1⁺ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.     

Revealing an unusual transparent phase of superhard iron tetraboride under high pressure

First principles–based electronic structure calculations of superhard iron tetraboride (FeB₄) under high pressure have been undertaken in this study. Starting with a “conventional” superconducting phase of this material under high pressure leads to an unexpected phase transition toward a semiconducting one. This transition occurred at 53.7 GPa, and this pressure acts as a demarcation between two distinct crystal symmetries, metallic orthorhombic and semiconducting tetragonal phases, with Pnnm and I4₁/acd space groups, respectively. In this work, the electron–phonon coupling-derived superconducting T_c has been determined up to 60 GPa and along with optical band gap variation with increasing pressure up to 300 GPa. The dynamic stability has been confirmed by phonon dispersion calculations throughout this study.The shorter interatomic distances of metal under external pressure consequently increase the valence and conduction band widths, which leads to the enhancement of free electron-like behavior. The development of creating immensely substantial pressure at laboratories enables us to observe the core electrons overlapping under enormous compression and dramatically influences the electronic properties of normally free electron metals such as Li and Na (1–3). The metal-to-insulating phase transformation has been contrived both experimentally and theoretically for both the normal metals while exerting pressure on them. This observation propelled us to investigate the electronic and structural phase transformation of the experimentally synthesized superhard material iron tetraboride (FeB₄) under high pressure (4–8). The intriguing factor of choosing FeB₄ is that the material was proposed as a “conventional” Fe-based superconductor, in contradiction to the discovery of an “unconventional” Fe-based superconductor because of its large electron–phonon coupling. Here we report the exotic phase transition of FeB₄ from metal to semiconductor at 53.7 GPa, even though we started with the metallic orthorhombic phase Pnnm of FeB₄, which shows the superconducting temperature T_c up to 60 GPa. The new phase after 53.7 GPa has I4₁/acd space group symmetry with a finite fundamental band gap, which increases along with pressure monotonically. All of the considered structures have been tested to have a thermodynamic stability from phonon dispersion calculations. The reason behind the phenomena could be the overlap of atomic cores at higher pressure ranges, which increases the hybridization of valence electrons and their repulsive interactions with core electrons. The immediate technological outcome of this scenario of metal-to-semiconducting phase transition could be to search for a transparent state of a material that is a metal under ambient conditions. This drastic change of electronic and structural properties can be observed in other materials as well, and hence this can open a field of studying them from a high-pressure perspective.