基于分子对接虚拟筛选铜绿假单胞菌胞外酶exoS抑制剂的研究

铜绿假单胞菌是引起宿主防御机制受损患者严重感染的重要原因。胞外酶S(exoS)为铜绿假单胞菌III型分泌系统(T3SS)分泌的毒力因子之一,是维持细菌在宿主体内繁殖的重要步骤。因此,本文首先运用虚拟筛选的方法学研究,确定exoS的6GNJ靶点蛋白为应用于分子对接虚拟筛选的最佳对接模型。随后利用分子对接、结构相似性筛选和类药性评价等多种策略,从中药系统药理学数据库与分析平台(TCMSP)数据库中筛选出4个命中分子。分子对接显示MOL008550和MOL001870与exoS受体蛋白具有强氢键作用和疏水相互作用,表现出较高的结合亲和力,为前2位最佳命中分子。结合分子动力学模拟分析发现,MOL008550和MOL001870与exoS受体蛋白的复合物比参考化合物(F4W501)具有更有利的动态稳定性。结合自由能计算显示,MOL008550和MOL001870的结合自由能强于F4W501,且与exoS受体蛋白的作用方式和F4W501类似,主要为静电、疏水作用及范德华力促进两者间的结合,其可能对exoS表现出更高的抑制活性,为潜在的exoS靶向小分子抑制剂。虚拟筛选活性化合物并探究其与胞外酶S的互作模式及动力学稳定性,为开发新型的高效靶向exoS抑制剂提供了研究思路和物质参考。

Systematic review of nutrition screening and assessment in inflammatory bowel disease

BACKGROUND Malnutrition is prevalent in inflammatory bowel disease (IBD). Multiple nutrition screening (NST) and assessment tools (NAT) have been developed for general populations, but the evidence in patients with IBD remains unclear. AIM To systematically review the prevalence of abnormalities on NSTs and NATs, whether NSTs are associated with NATs, and whether they predict clinical outcomes in patients with IBD. METHODS Comprehensive searches performed in Medline, CINAHL Plus and PubMed. Included: English language studies correlating NSTs with NATs or NSTs/NATs with clinical outcomes in IBD. Excluded: Review articles/case studies;use of body mass index/laboratory values as sole NST/NAT;age<16. RESULTS Of 16 studies and 1618 patients were included, 72% Crohn’s disease and 28% ulcerative colitis. Four NSTs (the Malnutrition Universal Screening Tool, Malnutrition Inflammation Risk Tool (MIRT), Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NRT) and Nutrition Risk Screening 2002 (NRS-2002) were significantly associated with nutritional assessment measures of sarcopenia and the Subjective Global Assessment (SGA). Three NSTs (MIRT, NRS-2002 and Nutritional Risk Index) were associated with clinical outcomes including hospitalizations, need for surgery, disease flares, and length of stay (LOS). Sarcopenia was the most commonly evaluated NAT associated with outcomes including the need for surgery and post-operative complications. The SGA was not associated with clinical outcomes aside from LOS. CONCLUSION There is limited evidence correlating NSTs, NATs and clinical outcomes in IBD. Although studies support the association of NSTs/NATs with relevant outcomes, the heterogeneity calls for further studies before an optimal tool can be recommended. The NRS-2002, measures of sarcopenia and developments of novel NSTs/NATs, such as the MIRT, represent key, clinically-relevant areas for future exploration.

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.

Evolving screening and surveillance techniques for Barrett's esophagus

Barrett's esophagus(BE) is a change in the esophageal lining and is known to be the major precursor lesion for most cases of esophageal adenocarcinoma(EAC).Despite an understanding of its association with BE for many years and the falling incidence rates of squamous cell carcinoma of the esophagus, the incidence for EAC continues to rise exponentially. In association with this rising incidence, if the delay in diagnosis of EAC occurs after the onset of symptoms,then the mortality at 5 years is greater than 80%. Appropriate diagnosis and surveillance strategies are therefore vital for BE. Multiple novel optical technologies and other advanced approaches are being utilized to assist in making screening and surveillance more cost effective. We review the current guidelines and evolving techniques that are currently being evaluated.

Expanding beyond endoscopy: A review of non-invasive modalities in Barrett’s esophagus screening and surveillance

Barrett’s esophagus(BE)is a condition that results from replacement of the damaged normal squamous esophageal mucosa to intestinal columnar mucosa and is the most significant predisposing factor for development of esophageal adenocarcinoma.Current guidelines recommend endoscopic evaluation for screening and surveillance based on various risk factors which has limitations such as invasiveness,availability of a trained specialist,patient logistics and cost.Trans-nasal endoscopy is a less invasive modality but still has similar limitations such as limited availability of trained specialist and costs.Non-endoscopic modalities,in comparison,require minimal intervention,can be done in an office visit and has the potential to be a more ideal choice for mass public screening and surveillance,particularly in patents at low risk for BE.These include newer generations of esophageal capsule endoscopy which provides direct visualization of BE,and tethered capsule endomicroscopy which can obtain high-resolution images of the esophagus.Various cell collection devices coupled with biomarkers have been used for BE screening.Cytosponge,in combination with TFF3,as well as EsophaCap and EsoCheck have shown promising results in various studies when used with various biomarkers.Other modalities including circulatory microRNAs and volatile organic compounds that have demonstrated favorable outcomes.Use of these cell collection methods for BE surveillance is a potential area of future research.

A rapid absorbance-based growth assay to screen the toxicity of oligomer Aβ42 and protect against cell death in yeast

Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s disease.Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity,the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies.We have previously established and validated budding yeast,Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ.Using colony counting based methods,oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast.We have adapted this method for high throughput screening by developing an absorbance-based growth assay.We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells.This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.

Vision Screening in the Pediatrician’s Office

Objective: To assess current practices, attitudes, and perceived barriers toward pediatric vision screening. Patients and Methods: A link to a 9-question survey was electronically distributed to a national sample of 6000 pediatricians through Medical Marketing Services Inc. Data were collected using Survey Monkey. Results: Email open rate was 11%;37% of those who opened the email responded (225 respondents). Over ninety percent of respondents perform some type of vision screening at least yearly, although age at which screening began varied, with two thirds of respondents instituting formal vision screening after three years. Fifty eight percent of respondents were either extremely unsatisfied, unsatisfied or only somewhat satisfied with their current screening method. Preferred methods of screening and confidence of pediatricians in their ability to detect pathology varied for children under versus over age three. The least frequently used methods for all age groups were autorefraction and photoscreening. The most commonly reported barriers to screening were inadequate training (48%), time required for exam (42%), and inadequate reimbursement (32%). Conclusions: Perceived barriers to vision screening in the pediatrician office have been previously identified, and photoscreening and autorefraction have been identified as a possible means to circumvent them. In spite of the addition of new procedural codes, pediatricians continue to report similar barriers to screening.

Ishii评分在养老机构老年人肌少症筛查中的应用

目的评价Ishii评分在养老机构老年人肌少症筛查中的准确性,为养老机构老年人肌少症筛查提供适用性工具。方法对养老机构386名老年人应用Ishii评分进行肌少症筛查,以亚洲肌少症工作组推荐的肌少症诊断标准为参考,使用灵敏度、特异度及ROC曲线下面积等指标评价Ishii评分肌少症筛查效应。结果肌少症检出率为49.7%,其中男91人,女101人;男性Ishii评分ROC曲线下面积为0.844,95%CI为0.786~0.902,女性Ishii评分ROC曲线下面积为0.806,95%CI为0.748~0.863;男性和女性分别在以137和161分为截断值时,约登指数达到最高水平。结论Ishii评分对于养老机构老年人肌少症筛查具有较高的筛检价值。

The Reasons Why Women Do Not Participate in the Papsmear Screening and Testing Program in Sweden

Cervical cancer is the second most common type of cancer among women worldwide. In Sweden cervical cancer is the fifteenth most common cancer among women and accounts for 1.9 percent of all female cancers. The Swedish Pap smear screening program is enabling early detection of cell changes in order that treatment may be administered to prevent the development of cancerous cells. There are approximately four hundred and fifty cases of cervical cancer detected each year in Sweden and of these cases, approximately seventy five percent occur in women who do not participate in the screening and testing program. The purpose of this study was to illustrate and examine the reasons why women did not participate in the program even though they had received a notice that they had an appointment for a Pap smear test. In the study fourteen women from a district in the west of Sweden were interviewed. In order to analyse the interviews a qualitative content analysis according to Lundman and Graneheim was used. The analysis resulted in the development of three categories which were identified as communication, treatment and subterfuge (reasons or excuses for not participating). The theme of the study was the professional treatment of the women’s conditions. In the interviews the women emphasize the importance of professional treatment that is administered with respectful and sympathetic care throughout the whole healthcare system regardless of where and when the visit was conducted. Efficient organization and clear communication would minimize the inconvenience for the women during their visit.

The Phenomenon of High Hardness Values on the S-Phase Layer of Austenitic Stainless Steel via Screen Plasma Nitriding Process

The purpose of this study is to improve the surface properties of austenitic stainless steel using the double-folded electrode screen plasma nitriding (SPN) process. In general, the S-phase is well-known for its excellent properties such as improved hardness and wear resistance along with sustained corrosion resistance. The concentrated nitrogen via SPN process was injected to form S-phase with time at 713 K. This study was carried out under the conditions of 44 at% of nitrogen injection, which was higher than 25 at% known as the condition of no precipitation of S-phase formed by the SPN process, and 20 K higher than the maximum temperature without precipitation phase. The hardness analysis of stainless steel sample treated by the SPN process at 713 K showed a much higher value than the typical nitriding hardness at a depth of lower nitrogen than the maximum nitrogen concentration. The SPN 20 hr treated specimen showed the average value of 2339 HV while 40 hr showed the average value of 2215 HV. The result is attributed to the concentrated nitrogen formed in the SPN process reacting with the alloying elements contained in the base material to form fine precipitates, thus producing a synergy effect of the extreme hardening effect;that is, the movement of precipitates and dislocations due to the GP-zone (Guinier-Preston zone).

It's Closed In Triumph,'97 International Screen Special Printing Technology Exhibition

’97 Wuhan International Screen Special Printing Technology Exhibition was held from May 21—24, 1997 in Wuhan city,the capital of Hubei Province. 120 famous exhibitors from China, USA, Canada, Holland, Japan, Korea, and Hong Kong, Taiwan districts attended the Exhibition. The booth area was more than 5000 m^2.

Persistent Xerophthalmia in a Patient with Rheumatological Disease and Priiviary Sjogren’s Syndrome: Case Report from Northern Brazil

This case study aims to contribute to the literature in order to highlight the importance of this collaboration between medical specialties. A female patient R.N.N. F, age 66, from the city of Manaus, with a previous diagnosis of Sjogren’s syndrome in regular follow-up by the Rheumatology team at the Araujo Lima outpatient clinic and referred to the Ophthalmology sector for complementary evaluation related to visual discomfort. The fundoscopy performed in the patient was within normal limits, but the symptoms experienced by her proved to be an important clinical finding, which has ratified the need for regular and multidisciplinary follow-up. This report unequivocally demonstrates that even in the face of tests considered within the expected limits for a given population, the clinical presentation can be specific and particular for each analyzed individual. Early screening exams should contemplate the patient in a holistic and individualized way whenever possible.

DRAINMOD-S模型参数的全局灵敏度分析

为有效进行DRAINMOD-S模型参数的优选,更好地理解参数变化对模拟结果的影响,开展了模型参数灵敏度分析。以南通市九龙垦区暗管排水脱盐试验为例,采用Morris全局定性分析方法检测了DRAINMOD-S模型模拟土壤剖面含盐量时侧向饱和导水率Ksat、水动力弥散系数D、地表最大蓄水深度Sm、相对不透水层深度Im、排水系数Dr及地下水初始埋深W 6个参数的灵敏度。结果表明:Ksat对模拟结果影响最为显著,D、Sm和Dr次之,而W与Im影响最小;各个参数间的非线性作用存在差异,以Ksat最为显著。为保证模型模拟质量,对敏感性参数应提高现场测试精度,在模型运行时,对灵敏度大的参数应进行重点调整,同时也不可忽视非线性作用较强的参数,从而有效地指导模型的参数率定,提高模型的适用性。

油料植物光皮树SSR-PCR反应体系优化及引物筛选

建立稳定可靠的SSR-PCR反应体系、筛选具有多态性SSR引物,是木本油料植物光皮树分子标记辅助育种与良种选育的重要基础研究。为给SSR标记技术在光皮树遗传图谱构建、亲缘关系鉴定及分子育种等方面的应用研究奠定基础,利用"Cf-05"正反向引物,采用L16(45)正交试验设计和单因素试验相结合的研究方法,对影响光皮树SSR-PCR反应体系的主要因素(模板DNA、引物、d NTPs、Mg^(2+)、Taq聚合酶浓度及退火温度)进行了试验分析。试验结果表明,光皮树SSR-PCR总体积为15μL的最佳反应体系为:模板DNA用量37.5 ng,正反向引物浓度均为0.6μmol·L^(-1),d NTPs浓度为0.3 mmol·L^(-1),Mg^(2+)的浓度为1.5 mmol·L^(-1),Taq聚合酶用量为1.5 U,最佳退火温度为50℃。运用优化了的光皮树SSR-PCR反应体系,可从71对引物中筛选获得11对能适用于光皮树的SSR引物。研究结果表明,试验所建立的反应体系可进一步用于光皮树SSR遗传多样性分析、遗传图谱构建和分子标记辅助育种等方面的研究中。

产S-腺苷蛋氨酸酵母菌的诱变选育

以选育产S-腺苷蛋氨酸的高产酿酒酵母菌株为目标,利用常温常压等离子体和137 Csγ-射线对菌株进行诱变。通过5轮常温常压等离子体诱变和4轮γ-射线诱变,结合乙硫氨酸、制霉菌素抗性筛选,获得突变株AC-10,摇瓶发酵48 h,其S-腺苷蛋氨酸产量达到1.15 g/L,与出发菌株相比提高了130.0%。摇瓶发酵最适条件为30℃、初始pH 5.5。经5 L发酵罐分批补料发酵68 h,S-腺苷蛋氨酸产量达到5.62 g/L。

孕早期产前筛查孕妇血清ADAM12-S中位数倍数校正方法的建立

目的建立孕早期产前筛查孕妇血清解整合素金属蛋白酶12分泌型(a disintegrin and metalloprotease,ADAM12-S)中位数倍数的校正方法。方法随机选择2008年在本中心自愿参加孕早期唐氏综合征(DS)产前筛查并经随访证实分娩健康儿的孕妇孕8～13周血清样本577份,用时间分辨荧光免疫分析法检测血清ADAM12-S浓度。用SPSS 15.0软件构建ADAM12-S与孕龄间的回归关系,选最优模型计算中位浓度,得到ADAM12-S中位数倍数(multiple of the median,MoM)值。探讨MoM值与体重的关系,选取最优模型求出经体重调整后的MoM值。将ADAM12-S初始浓度与消除孕周和体重影响校正后的最终MoM值进行曲线拟合,选取最优模型最终得到ADAM12-S初始浓度与校正后MoM值的关系方程。结果 ADAM12-S中位数(Y)与孕周(t)呈正相关,经s曲线模型拟合后的中位数方程为:Y=e8.412-24.534/t;ADAM12-S MoM值中位数(Y)与体重中位数(z)存在负相关,经指数模型拟合后的方程为:Y=1.603*e-0.009*z;ADAM12-S初始浓度(X)与孕周和体重校正后的最终MoM值(Y)的关系方程为Y=0.036*X0.552。结论 ADAM12-S初始浓度与最终MoM值的关系方程的建立,对临床开展ADAM12-S筛查DS妊娠的研究有重要意义。

采用SROC曲线评价我国唐氏综合征产前筛查方法的效果

目的在通过收集20年来国内唐氏综合征产前筛查情况发表的文献,利用SROC曲线方法分析唐氏综合征产前筛查的效果。方法以"唐氏综合征"、"产前筛查"和"产前诊断"为主题词,对《中国生物医学文献数据库》1987～2007年20年的文献进行检索,纳入文献收集数据,利用SAS8.1软件制作SROC曲线。结果根据SROC曲线,可以分析其筛查方法的最佳临界点,可以比较同一筛查方法的不同研究以及比较不同的筛查方法的效果。结论SROC曲线方法可应用于唐氏综合征产前筛查方法的评价,其结果对筛查方法的正确选取有一定的意义。

MNS血型系统同种抗体的分布、性质与免疫史研究

目的探讨MNS血型系统同种抗体在我院抗体筛查试验阳性的发生率和临床意义。方法回顾性分析我院2013年6月至2015年4月抗体筛查试验阳性患者中存在MNS血型系统同种抗体患者的临床资料,对其输血史、妊娠史、疾病特点进行总结分析。结果对41 550例患者进行抗体筛查试验,阳性者509例(1.2%),其中69例(69/509,13.6%)为MNS血型系统同种抗体。在此69例中,抗-M 64例,占92.8%;抗-N 2例,占2.9%;抗-S 3例,占4.3%;平均年龄(46.2±16.9)岁,有妊娠史者22例(31.9%),有输血史者14例(20.3%)。结论由于Ig G性质的抗体可引起新生儿溶血病(HDN),故应在明确孕产妇抗体筛查实验中的抗体性质后,及时为患者选择抗原阴性的血液作为储备,以确保其输血安全。MNS血型系统同种抗体可通过输血刺激产生,对于反复输血及器官移植患者,应定期做抗体筛查实验,并保留其结果,当鉴定出有特异性的同种抗体时,应给予相应抗原阴性交叉配血相合血液,以保证输血的安全性。

高产S-腺苷甲硫氨酸酵母菌株的筛选

从土壤和酒曲中对产S-腺苷甲硫氨酸的酵母菌株进行了筛选,通过HPLC外标法测定得到8株产量较高的酵母菌株。对高氯酸细胞破壁和酵母细胞水解作用条件进行优化,确定了高氯酸提取S-腺苷甲硫氨酸的理想条件为2.5mol/L高氯酸10mL,时间为5h,菌体量为0.6g。

莱文征结合TIMI危险评分对急性胸痛患者的筛选急性冠脉综合征(ACS)的研究

目的：莱文征结合心肌梗死溶栓疗法危险评分（TIMI 危险评分）与单独运用 TIMI 危险评分比较，探讨两种方法在急性胸痛患者筛选急性冠脉综合征（ACS）的临床价值。方法对171例胸痛患者随机分成试验组81例（TIMI 危险评分＋莱文征阳性）与对照组90例（TIMI 危险评分），根据患者的 TIMI 危险评分值，将其分成低分组（0～2分）、中分组（3～4分）与高分组（5～7分），在3个分值段内分别比较单独应用 TIMI 危险评分与 TIMI危险评分联合莱文征阳性对 ACS 发生率的差异性。结果TIMI 危险评分低分组中，用试验组方法13例，3例诊断为 ACS，筛查率为23．08％，用对照组方法11例，2例诊断为 ACS，筛查率为18．18％。两者进行χ2检验，差异无统计学意义（P ＞0．05）；TIMI 危险评分高分组患者中，用试验组方法41例，33例诊断为 ACS，筛查率为80．49％，用对照组方法46例，35例诊断为 ACS，筛查率为76．09％，进行χ2检验，差异无统计学意义（P ＞0．05）；在 TIMI危险评分中分组（3～4分）患者中，用试验组方法27例，20例诊断为 ACS，筛查率为74．07％。用对照组方法33例，17例诊断为 ACS，筛查率为51．52％。两者进行χ2检验，差异有统计学意义（P ＜0．05）。在中分组中，运用TIMI 危险评分联合莱文征与冠脉造影术这一金指标进一步比较后，发现运用 TIMI 危险评分联合莱文征诊断ACS 的敏感性为86．84％，特异性为90．91％，诊断符合率为88．33％（P ＜0．001）。结论TIMI 危险评分结合莱文征后，在中分组急性冠脉综合征的发生率比单独运用 TIMI 危险评分的发生率高，与单独运用 TIMI 危险评分系统相比，可以更好地预测 ACS 的发生，可以作为在急性胸痛患者筛选急性冠脉综合征的一项简单、有效工具。