基于特征的深度学习预测化合物-蛋白质相互作用的研究进展

药物研发过程中,化合物-蛋白质相互作用（compound-protein interaction,CPI）预测是发现苗头化合物、药物重定位等研究的关键技术手段。近年来,深度学习被广泛应用于CPI研究,加速了药物发现中CPI预测的发展。本文重点讨论基于特征的 CPI 预测模型,首先,介绍了CPI预测中常见的数据库、化合物和蛋白质的典型特征表示方法。根据建模中的关键问题,从多模态和注意力机制两个方面,对基于特征的CPI预测模型展开论述。在此基础上,选取其中12个模型,在3个经典数据集上评估了模型在分类任务和回归任务中的性能。本文总结当前该领域面临的挑战,对未来的发展方向进行展望,为CPI预测方法进一步研究提供思路。     

Accumulation and effects of lead and cadmium on wood ducks near a mining and smelting complex in Idaho

A study of wood ducks (Aix sponsa) was conducted along the Coeur d'Alene River system in northern Idaho in 1986 and 1987. Most of this area has been subjected to severe contamination from lead and other metals from mining and smelting since the 1880s. In 1986, a preliminary study of wood duck nesting was conducted in the contaminated area; incubating hens captured in nest boxes were bled and weighed. Blood samples were used to determine lead and cadmium concentrations and physiological characteristics. In 1987, an intensive study of wood ducks involved trapping and monitoring nest boxes in the contaminated area. Blood and tissue samples were also taken from wood ducks from a reference area without known contamination from metals. Lead levels in blood and tissues of most wood ducks from the contaminated area frequently exceeded those considered hazardous to birds; maximum levels (wet weight) of lead were 8 g g^–1 in blood and 14 g g^–1 in liver. Changes in physiological characteristics constituted the only evidence of potentially adverse effects from lead. In the contaminated area, nesting success (55% unadjusted, 35% Mayfield estimate) was less than in other areas where predation was low and nest boxes were used; but lead concentrations and physiological characteristics of blood were similar in successful and unsuccessful hens.Values of ALAD, hemoglobin, and body mass were negatively correlated with blood concentrations of lead, whereas protoporphyrin was positively correlated with lead levels in the blood. Some of the protoporphyrin values (1,091 g dl^–1 in a male and 756 g dl^–1 in a female) equalled those associated with lead toxicosis in experimental birds. ALAD activity was low in most birds from the contaminated area; values of 0 were obtained from 11 birds. Lead levels in blood, ALAD, protoporphyrin, and hemoglobin were significantly different between birds from the contaminated and reference areas. Concentrations of lead in ingesta of wood ducks ranged from 0.9 to 610 g g^–1 in the contaminated area and 0.2 to 0.6 g g^–1 in the reference area. Levels of cadmium in kidneys of wood ducks ranged from 1g g^–1 to 20 g g^–1 in the contaminated area and from only to 0.1 g g^–1 to 1 g g^–1 in the reference area. Cadmium concentrations were less than known effect levels.     

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

Wistar rat pups were administered either a high dose of lead acetate (400 g lead/g body weight/day) or a low dose (100 g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.     

严重开放性胫腓骨骨折两种固定法的比较与选择

目的：就钢板内固定与外固定架对严重开放性胫腓骨骨折的治疗结果进行比较分析。方法：２４１例病人,共２５６侧肢体,均为Ⅲ度胫腓骨骨折。用钢板内固定１７４侧,用外固定架６６例,一期截肢１６侧肢体。结果：钢板内固定组一期创面感染率１２．９％,二期创面感染率２１．０５;外固定架组一期创面感染率１３．６４％,二期创面感染率１８．１８％。两种固定法二期创面肉芽长满时间,钢板内固定组（ｎ＝１９）：３周以内６例,占     

Children's Health and the Environment—The First Herbert L. Needleman Award Lecture

Children today are exposed extensively to toxins in the environment. Prominent among these are exposures to over 70,000 synthetic chemicals, all newly developed in the past 50 years and largely untested for their hazards to children's health. Children are uniquely vulnerable to toxins, and with increasing incidence they are developing chronic, disabling, life-threatening diseases known or suspected to be of environmental origin–asthma, endocrine disruption, cancer, and the diseases caused by tobacco. Pediatricians need to consider toxic etiologies in the differential diagnosis of childhood illness.     

ROC曲线在评价铅中毒指标中的应用

目的评价几种铅中毒指标筛选不同水平职业性铅接触的准确性。方法连续性收集１５７名铅接触工人的血标本,同时测定血铅、红细胞游离原卟啉（ＦＥＰ）、锌原卟啉（ＺＰＰ）、尿铅、尿δ氨基酮戊酸（δＡＬＡ）,以血铅≥４０、≥６０μｇ／ｄｌ的铅接触水平为金标准,用ＲｅｃｅｉｖｅｒＯｐｅｒａｔｉｎｇＣｈａｒａｃｔｅｒｉｓｔｉｃ（ＲＯＣ受试者工作特征）曲线分析软件评价所测定指标筛选血铅≥４０、≥６０μｇ／ｄｌ职业性铅接触的价值,在ＲＯＣ曲线上制定各测定指标筛选上述２个铅接触水平的最佳临界点,用ＥＰＩＮＦＯＲ统计软件比较筛选血铅≥４０、≥６０μｇ／ｄｌ的平行试验的敏感度。结果筛选血铅≥４０、≥６０μｇ／ｄｌ的铅接触水平,ＲＯＣ曲线下的面积（ＡＵＣＲＯＣ）最大的是ＺＰＰ,其他依次为ＦＥＰ、尿铅、尿δＡＬＡ;联合ＺＰＰ与ＦＥＰ的平行试验的敏感度高于联合尿铅与尿δＡＬＡ的平行试验。结论筛选血铅≥４０、≥６０μｇ／ｄｌ水平的职业性铅接触,ＺＰＰ的准确性最高,并且联合ＺＰＰ与ＦＥＰ的平行试验的敏感度高于联合尿铅与尿δＡＬＡ的平行试验。     

上海市静安区(部分)儿童血铅水平状况调查

目的了解本地区儿童血铅水平现状。方法于１９９７年８月对静安区４３７例１４个月～５岁８个月的儿童进行血铅水平测定,并对每个入选儿童进行问卷调查,问卷涉及有关儿童个人情况及家庭、社会、环境等问题。结果４３７名儿童血铅水平从１５μｇ／Ｌ至６９７μｇ／Ｌ,血铅水平均数为９７．０４μｇ／Ｌ,其中血铅水平≥１００μｇ／Ｌ有１６７例,占３８．２％。本区儿童血铅水平低于工业区,高于远郊乡村,差异有显著性意义,小儿每日在马路上的时间长短为诸多影响因素中突出并存在显著性差异的因素。结论静安区虽为非工业区,但目前情况不容乐观,环境中的铅污染问题相当严重。对儿童和家长进行健康教育,规范家长和儿童的行为,是最有效、最廉价的降低儿童铅中毒患病率的方法。     

Precision and intersite correlation of bone densitometry at the radius, tibia and femur with peripheral quantitative CT

Objective. To compare the in situ precision of peripheral quantitative CT (pQCT) at the radius, tibia and femur, and to analyze the intersite correlation, in order to determine whether measurements at the lower extremity reproduce results at the radius or are of additional informative value. Design and material. pQCT measurements were performed in 86 elderly cadavers (mean age 80.5 years) at trabecular and cortical locations in the radius, tibia and femur, determining densitometric (bone mineral content and density) as well as geometric parameters (cross-sectional area, cortical thickness, polar moment of inertia and others). In 14 cadavers, repeated measurements were obtained at all sites on four different days. Results and conclusions. At cortical sites, the precision for the densitometric and geometric variables ranged from 0.4% to 4.3%, and was similar for the radius, tibia and femur. At trabecular locations, the reproducibility of the density measurements ranged from 1.8% to 2.5% at the radius, and from 3.2% to 5.9% at the femur and tibia. The intersite correlation of the total bone mineral content ranged from 0.87 and 0.97 at cortical sites, and from 0.63 to 0.85 at trabecular locations. The trabecular density showed a higher similarity between the tibia and femur (r=0.68–0.78) than between the radius and the lower extremity (r=0.41–0.45). The results demonstrate a substantial heterogeneity of trabecular bone in elderly individuals and advocate measurements directly at the site of clinical or scientific interest. Received: 5 July 1999 Revision requested: 12 August 1999 Revision received: 31 August 1999 Accepted: 13 September 1999     

Urinary lead as a possible surrogate of blood lead among workers occupationally exposed to lead

Objectives: The aim of the present study is to investigate whether lead (Pb) in urine (Pb-U) can be a valid surrogate of lead in blood (Pb-B), the traditional biomarker of exposure to lead in occupational health. Methods: Blood and spot urine samples were collected from 258 workers of both sexes occupationally exposed to lead. The samples were analyzed for lead by graphite furnace atomic absorption spectrometry, and the correlation between Pb-B and Pb-U was examined by linear regression analysis before and after logarithmic conversion. Results: The correlation coefficient (0.824; P < 0.01) was largest when the relationship between Pb-B and Pb-U was examined with 214 cases of one sex (i.e., men) after Pb-U was corrected for a specific gravity (1.016) of urine (Pb-Usg) and both Pb-B and Pb-Usg were converted to logarithms. The geometric means (GMs) of Pb-B and Pb-Usg for the 214 men were 489 μg/l and 81 μg/l, respectively. When Pb-Usg was assumed to be 100 μg/l in this set of correlations, the 95% confidence range of Pb-B for the group mean was narrow, i.e., 543–575 μg/l (with GM of 559 μg/l), whereas that for individual Pb-B values was as wide as 355–881 μg/l. Conclusions: The correlation of Pb-U with Pb-B among workers occupationally exposed to Pb was close enough to suggest that Pb-U may be a good alternative to Pb-B on a group basis, but not close enough to allow Pb-U to predict Pb-B on an individual basis. Received: 6 April 1999 / Accepted: 17 July 1999