血浆D-二聚体与纤维蛋白原检测结合超声检查对盆腔手术后下肢深静脉血栓的早期评价价值

目的 研究血浆D-二聚体（D-dimer）与纤维蛋白原（FIB）的动态变化对早期预测盆腔手术后下肢深静脉血栓（DVT）的意义,探讨彩色多普勒超声检查对患者DVT的早期诊断价值。方法 选取2014年1月至2016年1月在首都医科大学附属北京潞河医院妇科择期行盆腔手术并具有DVT高危因素的231例患者为研究对象,术前所有患者下肢深静脉彩色多普勒超声检查均为阴性。根据患者术后72~120 h下肢彩色多普勒超声检查结果,将患者分为血栓组（n=36）和非血栓组（n=195）。所有患者于手术前、术后第1天和术后第3天晨检测D-dimer和FIB,并进行统计分析。结果 血栓组与非血栓组比较,术后D-dimer和FIB显著增高,差异有统计学意义（P<0.05）,与术前比较,两组患者术后D-dimer和FIB显著增高,差异有统计学意义（P<0.05）。结论 血浆D-dimer、FIB检测结合彩色多普勒超声检查对妇科盆腔术后患者并发下肢DVT的早期诊断具有重要价值。     

基于文献计量学和内容分析法的腹针研究现状与趋势分析

目的 分析目前已发表的腹针文献,了解腹针研究的现状、存在问题及未来趋势,为该领域的研究和治疗工作提供参考.方法 对国内外数据库进行全面检索,采用文献计量法和内容分析法了解文献内、外部特征.结果 最终获得目标文献1 356篇.腹针疗法已成为热点,但我国不同地区发展不均衡;相关研究涉及医、教、研等多个领域,可治疗疾病143种,颈椎病、腰椎间盘突出症等的研究尤为突出;研究类型以RCT/CCT居多(669篇);已发布腹针国家标准1项、出版专著4部.结论 腹针在临床、科研、教学等方面有非常好的发展,应进一步加强高质量循证研究、建立实践指南等工作,更好地为医疗保健服务.     

Functional consequences of sequence variation in bundlin, the enteropathogenic Escherichia coli type IV pilin protein

The bundle-forming pilus (BFP) of enteropathogenic Escherichia coli (EPEC) is an important virulence factor. We examined the role of divergent alleles of bfpA encoding bundlin, the BFP pilin protein, in pilus biogenesis, pilus interactions, and immune responses. We found that the BFP biogenesis machine from an EPEC strain that expresses one bundlin type is capable of assembling all other bundlin types. Furthermore, we found that EPEC strains expressing divergent bundlin types are capable of forming mixed autoaggregates, suggesting that different pilin types can intertwine. However, we found that there was a marked difference between alleles in immunogenicity in both rabbits and mice of a peptide derived from a region of bundlin undergoing apparent diversifying selection. In addition, despite a high degree of cross-reactivity between divergent bundlin proteins, in both mice and rabbits responses appeared to be stronger against the homologous pilin protein than against the heterologous protein. This result was verified using sera from a volunteer study, which demonstrated that the human antibody responses after an initial challenge with live EPEC were stronger against the homologous bundlin protein than against a divergent bundlin protein. However, a repeat challenge induced equivalent responses. These results are consistent with the hypothesis that human immune responses against bundlin exert selective pressure on bfpA sequence divergence.     

A novel domain antibody rationally designed against TNF-alpha using variable region of human heavy chain antibody as scaffolds to display antagonistic peptides

Neutralizing of TNF-alpha has been proved effective in treatment of some autoimmune diseases, e.g. rheumatoid arthritis and Crohn's disease. Low molecular weight synthetic peptides can mimic the binding sites of TNF-alpha receptors and block the activity of TNF-alpha. In order to stabilize the conformation, increase the affinity and bioactivity, in this study, heavy chain variable region of human antibody was used as a scaffold to simultaneously display three peptides, which were designed on the interaction between TNF-alpha and it's neutralizing monoclonal antibody. On the basis of the structural character and physical-chemical property of the families of seven kinds of heavy chain variable regions (VH) in human antibodies, the fifth type of VH was screened as scaffold to display the antagonist peptide. Based on the computer-guided molecular design method, a novel domain antibody against TNF-alpha (named as ATD5) was designed as TNF-alpha antagonist. The theoretical study showed that ATD5 was more stable than displayed antagonist peptide. The binding activity with TNF-alpha was higher than free peptides. After expression and purification in Escherichia coli, ATD5 could bind directly with TNF-alpha and inhibit the binding of TNF-alpha to its two receptors, TNFR1 and TNFR2. ATD5 could also reduce the TNF-alpha-mediated cytotoxicity and inhibit TNF-alpha-mediated caspase activation on L929 cells in a dose dependent manner. The activity of ATD5 was significantly stronger than three peptides displayed by ATD5. This study provides a novel strategy for the development of new TNF-alpha inhibitors. This study demonstrates that it is possible to screen potential antagonists of TNF-alpha using in vitro analysis systems in combination with the computer-aided modeling method.     

Attenuated dengue 2 viruses with deletions in capsid protein derived from an infectious full-length cDNA clone

A full-length cDNA clone (pD212) of dengue virus type 2 isolated in China (DEN2-43) was constructed. Based on this, we constructed several mutants with deletions in capsid protein C using fusion PCR. These deletions removed part or almost all of the internal stretch of hydrophobic amino acid residues that is probably involved in virion assembly. We thus obtained viable mutant viruses. The propagation capacity of the mutant viruses in cell culture was impaired in parallel with the increasing size of the deletion, and the infectivity of mutant C(Delta42-59), from which all of helix III of capsid protein C was removed, was completely abolished. More importantly, the mutant viruses were highly attenuated in suckling mice but induced high levels of antibodies in adult mice. This study indicates that the structural and functional flexibility of capsid protein C make it a candidate target for the attenuation of dengue virus, which could open a promising new avenue for the development of live attenuated dengue vaccines.     

Impact of long-term exposure to local PM<Subscript>10</Subscript> on children’s blood pressure: a Chinese national cross-sectional study

The evidence of the effect of long-term exposure to particulate matter with aerodynamic diameter?≤?10 μm (PM₁₀) on children’s blood pressure is insufficient. We collected the data of systolic and diastolic blood pressure (SBP and DBP) for 71,763 children aged 7 to 18 from 30 cities from 2010 Chinese National Survey on Students’ Construction and Health, and the data of local annual average concentrations of PM₁₀, SO₂, NO₂, annual average of relative humidity, and ambient temperature from China Meteorological Administration and Ministry of Environment Protection of China. We used the generalized additive model (GAM) to estimate the associations between PM₁₀ exposure and children’s blood pressure. We found that there was a distinct geographic variation in the annual average concentrations of PM₁₀, ranging from 40 μg/m³ in Haikou to 155 μg/m³ in Lanzhou. After adjusting for individual characteristics, social economic conditions, ambient temperature, relative humidity, NO₂, and SO₂, we found that the increase of PM₁₀ was associated with increase of SBP and DBP in Chinese children. A 100-μg/m³ increase of PM₁₀ was associated with 0.88 mmHg (95% CI 0.71, 1.05) higher SBP and 0.91 mmHg (95% CI 0.77, 1.06) higher DBP (p <?0.001). Consistent associations of SBP or DBP with PM₁₀ were found in both girls and boys. We also found a larger estimated effect of PM₁₀ on SBP and DBP in overweight children than that in normal ones. Public health policy for improving the air quality could be helpful to protect children’s cardiovascular health.     

Effects of safflower injection on the pharmacodynamics and pharmacokinetics of warfarin in rats

1.?Safflower injection (SI) is extracted from Chinese herbal medicine safflower that comprises many active components. Warfarin is a common anticoagulant and has exhibited drug interactions with several herbal products. This study aimed to investigate the effects of SI on pharmacodynamics and pharmacokinetics of warfarin in rats.

2.?Wistar rats were randomly divided into blank control group, SI group, warfarin control group and SI?+?warfarin group, respectively. In SI and SI?+?warfarin groups, rats were injected with SI (1.6?mL/kg/d, i.p.) for 14?days. Warfarin (0.2?mg/kg) was given orally on the eighth day. Saline was given as control. The blood samples were collected at various time points. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. UPLC-MS/MS was used to determine the plasma concentrations of S(R)-warfarin, and the pharmacokinetic parameters were calculated.

3.?PT, APTT in SI and SI?+?warfarin rats increased significantly compared with corresponding control rats. The pharmacokinetic parameters including C_max, t_1/2, AUC_0-t and AUC_0-∞ of S-warfarin and R-warfarin in SI?+?warfarin rats were higher than those in warfarin control rats.

4.?These findings suggest that SI significantly increases the anticoagulant effect of warfarin by affecting its pharmacodynamic and pharmacokinetic parameters.