Site-specific mutagenicity of stereochemically defined 1,N2-deoxyguanosine adducts of trans-4-hydroxynonenal in mammalian cells

Trans-4-hydroxynonenal (HNE) is a toxic compound produced endogenously during lipid peroxidation. HNE is a potent electrophile that is reactive with both proteins and nucleic acids. HNE preferentially reacts with deoxyguanosine to form four stereoisomeric HNE-deoxyguanosine (HNE-dG) adducts: (6R, 8S, 11R), (6S, 8R, 11S), (6R, 8S, 11S), and (6S, 8R, 11R). These adducts were synthesized into 12-mer oligodeoxynucleotides, inserted into a DNA shuttle vector and evaluated for the ability of each stereoisomer to induce mutagenesis when replicated through mammalian cells. The resultant mutagenicity of these adducts was related to their stereochemistry, in that two of the HNE-dG adducts, (6R, 8S, 11R) and (6S, 8R, 11S), were significantly more mutagenic than the (6R, 8S, 11S) and (6S, 8R, 11R) HNE-dG adducts. These data conclusively demonstrate that HNE-derived DNA adducts can be mutagenic in mammalian cells and their ability to cause mutations is dictated by their stereochemistry.     

CTT triplex系统各基因座位等位基因在葡萄胎基因组中的分布及其意义

我们对采用PCR和聚丙烯酰胺凝胶电泳鉴别出的37例DNA完全来自父方的遗传学完全性葡萄胎(g-CHM)进行基因组中CTTtriplex系统各基因座位(CSF1PO、TPOX和TH01)等位基因分布的分析,并初步研究了这些等位基因分布与临床预后的关系。结果显示,在37例g-CHM中,CSF1PO座位中3个等位基因(11,12和14)和TPOX座位中的1个等位基因(11)的出现率与它们在北京地区人群中的基因频率差异显著;g-CHM中CSF1PO、TPOX和TH01基因座位杂合度显著低于北京地区人群的杂合度(P值均远小于0.01);在23例良性g-CHM和10例侵袭性g-CHM中:CSF1PO座位的等位基因10、11在良性中的出现率高于在侵袭性g-CHM中(P=0.026148),等位基因12在良性中的出现率低于在侵袭性g-CHM中(P=0.023879);TPOX座位的等位基因8在良性中的出现率高于在侵袭性g-CHM中(P=0.004322),而等位基因11在良性中的出现率低于其在侵袭性g-CHM中(P=0.008671)。上述结果提示,葡萄胎基因组中存在某些等位基因分布与在人群中的分布不同,而且葡萄胎是否具有侵袭性也和某些等位基因的出现率过高或过低有相关性,这些与侵袭性有关的等位基因可能成为预测葡萄胎是否具有侵袭性的标志物。     

湖南省两地区成瘾物质使用状况调查报告：使用率及相关因素

本文采用整群抽样的方法，对湖南两地区城乡共２３７７人（１５岁以上）的成瘾物质使用状况进行调查，其中男１１７９（４９．６％）人，女１１９９（５０．４％人），平均年龄男女分别为４１．２（ＳＤ＝１７．５）和４３．４（ＳＤ＝１８．６）。结果表明，饮酒率男性为５７．５％，女性为１７．３％，吸烟率男女分别为６８．２％和１１．７％；饮酒者多集中在每月饮１次左右的人群中（男５７．９％，女７７．９％），但吸烟者多集中在每日吸２０支及以上（男５２．４％，女４２．９％）的人群中。除解热镇痛剂外，男性各种精神活性物质的使用频率及剂量皆男高于女性，开始使用的年龄及成瘾的年龄男性低于女性；性别、使用频度、最早使用的年龄、婚姻与饮酒、吸烟量关系最为密切。有１４人使用过鸦片类物质，４人使用过兴奋剂。作者讨论了我国成瘾物质使用的特点，指出经济水平、社会文化背景等因素与我国社会性成瘾物质的使用有密切关系。     

Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment

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Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

Radioprotective Effect of Whey Hydrolysate Peptides against γ-Radiation-Induced Oxidative Stress in BALB/c Mice

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against ⁶⁰Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.     

颅脑创伤急性期外周血白细胞变化的临床意义

目的 探讨颅脑创伤急性外周血白细胞（PWBC）数及中性粒细胞（PMN）比例与病情及预后的关系。方法 回顾性分析总结50例颅脑创伤急性期外周血白细胞数及性粒细胞比例,根据病情或预后分组分别进行比较。结果 颅脑创伤病情重者较病情轻者PWBC数与PWM比例显著提高（P＜0．05,P＜0．001）;恢复不良组及死亡组与恢复良好组相比,PWBC数显著增高（P＜0．05,P＜0．01）。结论 临床监测PWBC数及PMN比例可作为颅脑创伤患者的病情判断和预后估计的一项辅助指标。