连续性血浆滤过吸附对严重感染合并MODS患者炎症因子水平的影响

目的:探讨连续性血浆滤过吸附对严重感染合并多脏器功能障碍综合征(MODS)患者炎症因子水平的影响。方法:研究对象选取我院2013年3月-2016年3月收治严重感染合并MODS患者共160例,以随机数字表法分为对照组(80例)和观察组(80例),患者均先给予高容量血液滤过(HVHF)治疗,观察组加用连续性血浆滤过吸附辅助治疗,比较两组患者治疗前后平均动脉压(MAP)、心率(HR)、血氧饱和度(SpO_2)、碳酸氢根(HCO_3~-)、肌酐(Scr)、总胆红素(TBi L)、急性生理与慢性健康II(APACHE Ⅱ)评分、肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP)及白介素6(IL-6)水平。结果:两组治疗后MAP、Scr、TBi L、TNF-α、IL-6、hs-CRP及APACHE Ⅱ评分均有所降低,而HR、SpO_2、HCO_3~-水平均上升,且观察组以上各指标改善更明显,差异均有统计学意义(P0.05)。结论:连续性血浆滤过吸附辅助治疗严重感染合并MODS可有效稳定生命体征,改善生化指标,延缓病情进展,并有助于降低机体炎症反应水平。     

On-farm assessment of laying hen welfare: a comparison of one environment-based and two animal-based methods

Methods available to assess animal welfare at farm level are based on a range of welfare parameters, which can be divided into two categories, environment-based and animal-based parameters. The first category describes features of the environment and management, which can be considered prerequisites for welfare. The second category records animals’ responses to that particular environment and management more directly. Objective of this study was to validate a mainly environment-based method, the animal needs index (ANI), with animal-based methods: behavioural observations and feather condition scores (FCS). The study was conducted on 20 commercial laying hen farms, 10 farms with battery cages and 10 farms with deep litter systems. During a 1-day visit on each farm, ANI was assessed, FCS was scored, and behavioural observations were performed. Instantaneous scan sampling and continuous focal sampling were used to assess the time spent on different behaviours and the occurrence of event behaviours. Data from behavioural observations and FCS were reduced with principal factor analysis. This resulted in two factors for each method. Significant positive correlations were found between ANI, on the one hand, and ‘movement’ and ‘comfort’, two factors from behavioural observations, on the other hand. A significant negative correlation was found between ANI and ‘wing damage’ (from FCS). The results of this study show that ANI is valid and sensitive enough to show differences in animal welfare between housing systems, whereas differences in welfare within housing systems cannot be shown. In conclusion, ANI is an appropriate method for assessment of laying hen welfare on a large number of farms with different housing systems.     

Scoring ligand similarity in structure‐based virtual screening

Scoring to identify high‐affinity compounds remains a challenge in virtual screening. On one hand, protein–ligand scoring focuses on weighting favorable and unfavorable interactions between the two molecules. Ligand‐based scoring, on the other hand, focuses on how well the shape and chemistry of each ligand candidate overlay on a three‐dimensional reference ligand. Our hypothesis is that a hybrid approach, using ligand‐based scoring to rank dockings selected by protein–ligand scoring, can ensure that high‐ranking molecules mimic the shape and chemistry of a known ligand while also complementing the binding site. Results from applying this approach to screen nearly 70 000 National Cancer Institute (NCI) compounds for thrombin inhibitors tend to support the hypothesis. EON ligand‐based ranking of docked molecules yielded the majority (4/5) of newly discovered, low to mid‐micromolar inhibitors from a panel of 27 assayed compounds, whereas ranking docked compounds by protein–ligand scoring alone resulted in one new inhibitor. Since the results depend on the choice of scoring function, an analysis of properties was performed on the top‐scoring docked compounds according to five different protein–ligand scoring functions, plus EON scoring using three different reference compounds. The results indicate that the choice of scoring function, even among scoring functions measuring the same types of interactions, can have an unexpectedly large effect on which compounds are chosen from screening. Furthermore, there was almost no overlap between the top‐scoring compounds from protein–ligand versus ligand‐based scoring, indicating the two approaches provide complementary information. Matchprint analysis, a new addition to the SLIDE (Screening Ligands by Induced‐fit Docking, Efficiently) screening toolset, facilitated comparison of docked molecules' interactions with those of known inhibitors. The majority of interactions conserved among top‐scoring compounds for a given scoring function, and from the different scoring functions, proved to be conserved interactions in known inhibitors. This was particularly true in the S1 pocket, which was occupied by all the docked compounds. Copyright © 2009 John Wiley & Sons, Ltd.     

An Apgar scoring system for routine assessment of newborn puppy viability and short-term survival prognosis

The Apgar scoring system is an easy and reliable method for evaluating both human and animal neonates. However, its use is not widespread in veterinary medicine. The current study assessed a modified Apgar scoring system for routine evaluation of newborn puppies. Heart rate, respiratory effort, reflex irritability, motility, and mucus color have been evaluated in the score. Specifically, we used 5 min after birth Apgar score to assess newborn viability and short-term survival prognosis, as well as related characteristics, in 193 puppies from 42 litters, 65 born by spontaneous delivery, 66 by assisted delivery, and 62 by cesarean section. The percentage of puppies that were dead 2 h after birth was higher in the 4 to 6 Apgar score group versus that in the 7 to 10 score group (P < 0.01) and in the 0 to 3 score group versus that in the 7 to 10 score group (P < 0.0001). Delivery method did not affect survival. There was a marked reduction in the number of puppies searching for the mammary gland in the 0 to 3 and 4 to 6 Apgar score groups compared with that in the 7 to 10 score group (P < 0.0001); there was a difference between the 0 to 3 and the 4 to 6 score groups as well (P < 0.05). Suckling/swallowing reflexes were present in fewer puppies in the 0 to 3 and 4 to 6 score groups compared with that in the 7 to 10 group (P < 0.0001), with no significant differences between the 0 to 3 and the 4 to 6 score groups.     

An Ion-channel Modulator from the Saliva of the Brown Ear Tick has a Highly Modified Kunitz/BPTI Structure

Ra-KLP, a 75 amino acid protein secreted by the salivary gland of the brown ear tick Rhipicephalus appendiculatus has a sequence resembling those of Kunitz/BPTI proteins. We report the detection, purification and characterization of the function of Ra-KLP. In addition, determination of the three-dimensional crystal structure of Ra-KLP at 1.6 Å resolution using sulphur single-wavelength anomalous dispersion reveals that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by β-strands. Even more unusually, the N-terminal portion of the polypeptide chain is pinned to the ”Kunitz head” by two disulphide bridges not found in classical Kunitz/BPTI proteins. The disulphide bond pattern has been further altered by the loss of the bridge that normally stabilizes the protease-binding loop. Consistent with the conversion of this loop into a β-strand, Ra-KLP shows no significant anti-protease activity; however, it activates maxiK channels in an in vitro system, suggesting a potential mechanism for regulating host blood supply during feeding.     

Cliques in mitotic spindle network bring kinetochore‐associated complexes to form dependence pathway

The mitotic spindle is an essential molecular machine for chromosome segregation during mitosis. Achieving a better understanding of its organization at the topological level remains a daunting task. To determine the functional connections among 137 mitotic spindle proteins, a protein–protein interaction network among queries was constructed. Many hub proteins, which connect more than one query and serve as highly plausible candidates for expanding the mitotic spindle proteome, are ranked by conventional degree centrality and a new subnetwork specificity score. Evaluation of the ranking results by literature reviews and empirical verification of SEPT6, a novel top‐ranked hub, suggests that the subnetwork specificity score could enrich for putative spindle‐related proteins. Topological analysis of this expanded network shows the presence of 30 3‐cliques and six 4‐cliques (fully connected subgraphs) that, respectively, reside in eight kinetochore‐associated complexes, of which seven are evolution conserved. Notably, these complexes strikingly form dependence pathways for the assembly of the kinetochore complex. These analyses indicate the feasibility of using network topology, i.e. cliques, to uncover novel pathways to accelerate our understanding of potential biological processes.     

Effect of reproductive tract scoring on reproductive efficiency in beef heifers bred by timed insemination and natural service versus only natural service

The objective was to determine the effects of reproductive tract score (RTS) on reproductive performance in beef heifers bred by timed artificial insemination followed by natural service (AI-NS) or by natural service only (NSO). Angus cross beef heifers (n = 2660) in the AI-NS group were artificially inseminated at a fixed time (5- or 7-day CO-Synch + controlled internal drug release protocol) once, then exposed to bulls 2 weeks later (bull-to-heifer ratio = 1:40–1:50) for the reminder of the 85-day breeding season. Angus cross beef heifers (n = 1381) in NSO group were submitted to bulls (bull-to-heifer ratio = 1:20–1:25) for the entire 85-day breeding season. Heifers were reproductive tract scored from 1 (prepubertal) to 5 (cyclic) 4 weeks before, and were body condition scored (BCS) from 1 (emaciated) to 9 (obese) at the beginning of breeding season. Pregnancy diagnosis was performed 70 days after AI for AI-NS group and 2 months after the end of breeding season for both groups. Heifers in both groups were well managed and of similar age (14.9 ± 0.4 [AI-NS] and 14.7 ± 0.8 [NSO] months). Pregnancy rates (PRs) and number of days to become pregnant were calculated using PROC GLIMMIX and PROC LIFETEST procedures of SAS. Adjusting for BCS (P = 0.07), expressed estrus (P < 0.05), year (P < 0.05), and BCS by year interaction (P < 0.05), the AI-PR was greater for heifers in AI-NS group with higher RTS (P < 0.0001; 40.7%, 48.3%, 57.6%, and 64.6% for RTS of 2 or less, 3, 4, and 5, respectively). Controlling for BCS (P < 0.05), year (P < 0.05) and the breeding season pregnancy rates (BS-PRs) were greater for heifers in the AI-NS group with higher RTS (P < 0.01; 81.2%, 86.5%, 90.4%, and 95.2% for RTS of 2 or less, 3, 4, and 5, respectively). Similarly, adjusting for BCS, year (P < 0.05), the BS-PR was greater for heifers in NSO group with higher RTS (P < 0.01; 79.7%, 84.3%, 88.4%, and 90.2% for RTS of 2 or less, 3, 4, and 5, respectively). Heifers with higher RTS in both groups became pregnant earlier in the breeding season compared with heifers with lower RTS (log-rank statistics: P < 0.0001). Heifers in the AI-NS group become pregnant at a faster rate compared with those in the NSO group (P < 0.01). The BS-PR for heifers with RTS 5 was different between AI-NS and NSO groups (P < 0.0001). In conclusion, the RTS influenced both the number of beef heifers that became pregnant during the breeding season and the time at which they become pregnant. Furthermore, irrespective of RTS, heifers bred by NSO required more time to become pregnant than their counterparts in herds that used timed AI. The application of RTS system is reliant on the use of synchronization protocol. The application of RTS for selection may plausibly remove precocious females with lower RTS. On the contrary, application of RTS would help select heifers that will become pregnant earlier in breeding season.     

Kiwifruit extracts inhibit cytokine production by lipopolysaccharide-activated macrophages, and intestinal epithelial cells isolated from IL10 gene deficient mice

Inflammatory bowel disease (IBD) is a chronic, inflammatory disorder of the gastrointestinal tract involving an inappropriate immune response to commensal microorganisms in a genetically susceptible host. This study examined the effects of aqueous and ethyl acetate extracts of gold kiwifruit (Actinidia chinensis) or green kiwifruit (Actinidia deliciosa) using in vitro models of IBD. These models comprised primary macrophages and intestinal epithelial cells isolated from C57BL/5J and interleukin-10 gene deficient (Il10^−/−) mice and RAW 264.7, a murine macrophage-like cell line. All four kiwifruit extracts reduced the activation of these models after lipopolysaccharide stimulation, decreasing nitric oxide and cytokine secretion by both Il10^−/− and wild-type cells. The ethyl acetate extracts exhibited the highest anti-inflammatory activity, with almost complete suppression of lipopolysaccharide-stimulated macrophage activation. These results suggest that kiwifruit extracts have significant anti-inflammatory activity relevant to IBD. We suggest that the Il10^−/− mouse is a suitable model for further study of these compounds.     

复合凝乳酶对功能性消化不良儿童营养状态和摄食行为的影响

目的:观察复合凝乳酶胶囊对不同亚型功能性消化不良儿童临床表现、营养状态和摄食行为的影响及安全性。方法:以2017年8月至2018年9月在湖北省妇幼保健院儿童消化内科就诊的功能性消化不良(Functional dyspepsia,FD)儿童为研究对象进行问卷调查,观察治疗前和复合凝乳酶治疗2 w后患儿临床症状变化及药物相关不良反应的发生情况,监测患儿身高和体重,进行膳食情况的调查。结果:共163例儿童纳入研究,发生餐后不适综合征(Postprandial distress syndrome, PDS)66例,上腹痛综合征(Epigastric pain syndrome, EPS)97例。治疗前,PDS组儿童症状总分明显高于EPS儿童(6.9±2.7 vs 3.6±1.7,t=5.90,P=0.00)。PDS组儿童WAZ、WHZ、HAZ、身高别体质量Z值(weight for height Z score,WHZ)、年龄别身高Z值(height for age Z score,HAZ)、年龄别体质量Z值(weight for age Z score,WAZ)、体质量指数(body mass index,BMI)、膳食多样化分数(Dietary diversity score, DDS)均明显低于EPS组(P均0.05)。治疗2 w后,PDS儿童症状总分明显降低(P=0.00),改善程度依次为:厌食早饱腹痛嗳气恶心腹胀。EPS儿童症状总分无明显变化(P=0.11)。PDS儿童WAZ、WHZ、DDS均有明显升高(P均0.05)。EPS儿童DDS无明显变化(t=0.22,P=0.30)。研究期间未见明显药物相关不良反应。结论:复合凝乳酶胶囊可改善PDS患儿的临床症状、营养状态和膳食多样性,且安全性高。