球面对称设计结合遗传神经网络优选黄芪-红花药对水提工艺

目的采用球面对称设计及遗传神经网络优选黄芪-红花药对的水提工艺。方法将黄芪-红花药对水提液中8种有效成分(羟基红花黄色素A、紫丁香苷、毛蕊异黄酮苷、脱水红花黄色素B、山柰酚-3-O-芸香糖苷、芒柄花苷、毛蕊异黄酮、黄芪甲苷)的含量进行赋权,以计算得到的综合得分作为水提工艺的评价指标。在单因素实验基础上,选择液料比、提取时间、提取温度3个因素,依据球面对称设计进行实验,并结合遗传神经网络模型进一步优选黄芪-红花药对水提工艺参数。结果球面对称设计得到的最佳提取条件为液料比20∶1、提取时间30 min、提取温度87℃、提取次数2次,其综合评分为4.877;以遗传神经网络得到的最佳提取条件为液料比22.7∶1、提取时间30 min、提取温度87℃、提取次数2次,经验证该条件下的综合得分为5.004。实验结果显示,遗传神经网络能够提高水提工艺条件的综合评分。结论球面对称设计和遗传神经网络能够优化黄芪-红花药对水提工艺参数,可为中药及其制剂中多种有效成分提取的工艺优选提供参考。     

健脾益肺膏方治疗小儿反复呼吸道感染肺脾两虚、卫表不固证的临床疗效分析

目的观察健脾益肺膏方治疗小儿反复呼吸道感染(RRTI)肺脾两虚、卫表不固证的临床疗效,探析其运用于小儿RRTI预后的可行性。方法将84例RRTI肺脾两虚、卫表不固证患儿随机分为治疗组和对照组,每组42例。治疗组患儿给予健脾益肺膏方口服治疗,对照组给予脾氨肽口服冻干粉口服治疗,疗程为3个月。观察2组患儿治疗前后血中免疫球蛋白IgG、IgA、IgM水平的变化情况,并评价2组的临床疗效及安全性。结果(1)治疗3个月后,治疗组总有效率为95.24%(40/42),对照组为76.19%(32/42);治疗组疗效明显优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患儿的血中IgG、IgA和IgM水平均较治疗前明显提高(P<0.05),且治疗组对患儿血中IgG、IgA和IgM水平的作用均明显优于对照组,差异均有统计学意义(P<0.05)。(3)治疗组的不良反应发生率为2.38%(1/42),对照组为7.14%(3/42),组间比较,差异无统计学意义(P>0.05)。结论健脾益肺膏方治疗小儿RRTI肺脾两虚、卫表不固证疗效确切,可有效改善患儿临床症状,提高患儿免疫功能,且具有较高的安全性,可用于小儿RRTI的临床预后治疗。     

Box-Behnken设计-效应面法优化延胡索乙素聚乳酸-羟基乙酸共聚物纳米粒处方和体外释药行为研究

目的 Box-Behnken设计-效应面法（Box-Behnken design-response surface method,BBD-RSM）优化延胡索乙素（THP）聚乳酸-羟基乙酸共聚物[poly（lactic-co-glycolic acid）,PLGA]纳米粒（THP-PLGA-NPs）处方,并进行体外评价。方法 纳米沉淀法制备THP-PLGA-NPs,以包封率、载药量、多分散系数（polydispersity index,PDI）和粒径大小为评价指标,单因素结合BBD-RSM筛选最优处方,采用甘露醇作为冻干保护剂制备成冻干粉,将最优处方进行表征及体外释放实验。结果 最佳处方为PLGA用量为491.8 mg、油水体积比1：5.2、乳化剂质量分数为1.12%。THP-PLGA-NPS包封率为（185.07±1.06）%,载药量为（4.73±0.21）%,粒径为（181.32±7.14）nm,分别与模型预测值接近。体外释药具有明显的缓释特征,释药过程符合Higuchi模型：M_t/M_∞=0.112 4 t^1/2+0.078 0,r=0.987 9。结论 Box-Behnken实验设计可用于THP-PLGA-NPS处方的筛选,且优化后的纳米粒具有缓释作用。     

苦豆子SaLDC密码子偏好性分析、优化及原核表达

目的研究苦豆子SaLDC密码子偏好性、优化及原核表达。方法运用EMBOSS在线程序中的CHIPS、CUSP和CodonW软件分析SaLDC密码子的偏好性,根据大肠杆菌密码子的偏好性对SaLDC密码子进行优化,并将优化后的基因命名为optSaLDC;构建重组表达载体pET?28a(+)?optSaLDC,转化大肠杆菌BL21(DE3);IPTG诱导SaLDC蛋白表达,并对表达蛋白进行质谱分析。结果SaLDC有28个密码子的RSCU值>1.00,偏好使用以A/T结尾的密码子;SaLDC的密码子使用偏好性与拟南芥最接近,与大肠杆菌差别最大。优化后的optSaLDC在大肠杆菌中最佳表达条件为IPTG浓度1.0 mmol/L,诱导温度15℃,诱导时间16 h。LC?MS/MS鉴定诱导得到的SaLDC蛋白分子质量为48990.51 Da。结论诱导获得的optSaLDC纯化蛋白可用于后续体外SaLDC酶活性分析,为深入研究该基因的功能提供依据。     

黄芪多糖的不同提取优化工艺

目的：比较不同提取工艺的黄芪多糖提取率。方法：选用超声波辅助提取法对黄芪多糖进行提取,比较正交实验最优提取工艺和响应面试验最优提取工艺的提取率。结果：经由响应面优化得出：最优提取时间22 min,最优提取温度50 ℃,最优料液比16:1（mL/g）,理论提取率为9.93%;经过正交设计优化得出：最优提取时间20 min,最优提取温度40 ℃,最优料液比15:1（mL/g）,理论提取率为9.56%。结论：经二种优化结果进行验证比较,研究结果表明响应面法优化结果更为准确、合理,更适宜推广。     

Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study

Background

Valproic acid (VPA) has been shown to improve survival in animal models of hemorrhagic shock at a dose of 300 mg/kg. Our aim was to identify the ideal dose through dose-escalation, split-dosing, and dose de-escalation regimens.

Materials and methods

Rats were subjected to sublethal 40% hemorrhage and treated with vehicle or VPA (dose of 300, 400, or 450 mg/kg) after 30 min of shock. Acetylated histones and activated proteins from the PI3K–Akt–GSK-3β survival pathway at different time points were quantified by Western blot analysis. In a similar model, a VPA dose of 200 mg/kg followed 2 h later by another dose of 100 mg/kg was administered. Finally, animals were subjected to a lethal 50% hemorrhage and VPA was administered in a dose de-escalation manner (starting at dose of 300 mg/kg) until a significant drop in percent survival was observed.

Results

Larger doses of VPA resulted in greater acetylation of histone 3 and increased activation of PI3K pathway proteins. Dose-dependent differences were significant in histone acetylation but not in the activation of the survival pathway proteins. Split-dose administration of VPA resulted in similar results to a single full dose. Survival was as follows: 87.5% with 300 and 250 mg/kg of VPA, 50% with 200 mg/kg of VPA, and 14% with vehicle-treated animals.

Conclusions

Although higher doses of VPA result in greater histone acetylation and activation of prosurvival protein signaling, doses as low as 250 mg/kg of VPA confer the same survival advantage in lethal hemorrhagic shock. Also, VPA can be given in a split-dose fashion without a reduction in its cytoprotective effectiveness.     

Fast track surgery and preoperative optimization

Enhanced recovery pathways have been rapidly embraced by surgeons as a mechanism for improving patient care and driving down complications and costs. They seek to employ a holistic approach, reviewing all aspects of patient management, to improve care. Many components are dissimilar to traditional surgical teaching, involving early mobilization and enteral nutrition, as well as a strong emphasis on fluid balance and pain management. By addressing all components of the patient pathway from preoperative through to post-surgery, significant improvement in outcomes can be achieved for a range of surgical procedures.     

Burn resuscitation on the African continent

A survey of members of the International Society of Burn Injuries (ISBI) and the American Burn Association (ABA) indicated that although there was difference in burn resuscitation protocols, they all fulfilled their functions. This study presents the findings of the same survey replicated in Africa, the only continent not included in the original survey.One hundred and eight responses were received. The mean annual number of admissions per unit was ninety-eight. Fluid resuscitation was usually initiated with total body surface area burns of either more than ten or more than fifteen percent. Twenty-six respondents made use of enteral resuscitation.The preferred resuscitation formula was the Parkland formula, and Ringer's Lactate was the favoured intravenous fluid. Despite satisfaction with the formula, many respondents believed that patients received volumes that differed from that predicted. Urine output was the principle guide to adequate resuscitation, with only twenty-one using the evolving clinical picture and thirty using invasive monitoring methods. Only fifty-one respondents replied to the question relating to the method of adjusting resuscitation. While colloids are not available in many parts of the African continent on account of cost, one might infer than African burn surgeons make better use of enteral resuscitation.     

Comparing within‐subject classification and regularization methods in fMRI for large and small sample sizes

In recent years, a variety of multivariate classifier models have been applied to fMRI, with different modeling assumptions. When classifying high‐dimensional fMRI data, we must also regularize to improve model stability, and the interactions between classifier and regularization techniques are still being investigated. Classifiers are usually compared on large, multisubject fMRI datasets. However, it is unclear how classifier/regularizer models perform for within‐subject analyses, as a function of signal strength and sample size. We compare four standard classifiers: Linear and Quadratic Discriminants, Logistic Regression and Support Vector Machines. Classification was performed on data in the linear kernel (covariance) feature space, and classifiers are tuned with four commonly‐used regularizers: Principal Component and Independent Component Analysis, and penalization of kernel features using L₁ and L₂ norms. We evaluated prediction accuracy (P) and spatial reproducibility (R) of all classifier/regularizer combinations on single‐subject analyses, over a range of three different block task contrasts and sample sizes for a BOLD fMRI experiment. We show that the classifier model has a small impact on signal detection, compared to the choice of regularizer. PCA maximizes reproducibility and global SNR, whereas L_p‐norms tend to maximize prediction. ICA produces low reproducibility, and prediction accuracy is classifier‐dependent. However, trade‐offs in (P,R) depend partly on the optimization criterion, and PCA‐based models are able to explore the widest range of (P,R) values. These trends are consistent across task contrasts and data sizes (training samples range from 6 to 96 scans). In addition, the trends in classifier performance are consistent for ROI‐based classifier analyses. Hum Brain Mapp 35:4499–4517, 2014. © 2014 Wiley Periodicals, Inc .     

Flow disturbances generated by feeding and swimming zooplankton

Interactions between planktonic organisms, such as detection of prey, predators, and mates, are often mediated by fluid signals. Consequently, many plankton predators perceive their prey from the fluid disturbances that it generates when it feeds and swims. Zooplankton should therefore seek to minimize the fluid disturbance that they produce. By means of particle image velocimetry, we describe the fluid disturbances produced by feeding and swimming in zooplankton with diverse propulsion mechanisms and ranging from 10-µm flagellates to greater than millimeter-sized copepods. We show that zooplankton, in which feeding and swimming are separate processes, produce flow disturbances during swimming with a much faster spatial attenuation (velocity u varies with distance r as u ∝ r⁻³ to r⁻⁴) than that produced by zooplankton for which feeding and propulsion are the same process (u ∝ r⁻¹ to r⁻²). As a result, the spatial extension of the fluid disturbance produced by swimmers is an order of magnitude smaller than that produced by feeders at similar Reynolds numbers. The “quiet” propulsion of swimmers is achieved either through swimming erratically by short-lasting power strokes, generating viscous vortex rings, or by “breast-stroke swimming.” Both produce rapidly attenuating flows. The more “noisy” swimming of those that are constrained by a need to simultaneously feed is due to constantly beating flagella or appendages that are positioned either anteriorly or posteriorly on the (cell) body. These patterns transcend differences in size and taxonomy and have thus evolved multiple times, suggesting a strong selective pressure to minimize predation risk.Zooplankters move to feed, find food, and find mates, so moving is critical to the efficient execution of essential functions. However, moving comes at a predation risk: Swimming increases the predator encounter velocity (encounter rate increases with prey velocity to a power ≤1), and feeding and swimming generate fluid disturbances that may be perceived by rheotactic predators, thus increasing the predator’s detection distance (encounter rate increases with detection distance squared) (1–5). So, the advantages of moving and feeding must be traded off against the associated risks, and organisms should aim at moving and foraging in ways that reduce the predation risk and optimize the trade-off (6, 7). They may do so by moving in patterns that minimize encounter rates (8) and/or they may feed and propel themselves in ways that generate only small fluid disturbances (9). For example, theoretical models suggest that zooplankton that swim by a sequence of jumps may create a smaller fluid disturbance than similar-sized ones that swim smoothly (9), that a hovering zooplankter generates a larger fluid signal than one that cruises through the water (10, 11), and that a zooplankter moving at low Reynolds numbers will generate a relatively larger fluid signal than one moving at higher Reynolds numbers (11). Thus, motility patterns and propulsion modes may strongly influence predation risk and must be subject to strong selection pressure during evolution.Zooplankton span a huge taxonomic diversity and a large size range (from microns to centimeters) and their propulsion mechanisms vary substantially (12). Unicellular plankton may use one or more flagella or cilia, and the flagella may be smooth or plumose, which has implications for whether the cell is pulled or pushed by the beating flagellum (13). Ciliates may have the cilia rather evenly distributed on the cell surface or concentrated on certain parts of the cell, typically either anteriorly or as an equatorial band. Small animals may have an anterior “corona” of cilia (e.g., rotifers and many pelagic invertebrate larvae) to generate feeding currents and propulsion, or they may have beating or vibrating appendages that can be positioned anteriorly, ventrally, or laterally. The implications and potential adaptive value of this diversity of propulsion modes for feeding and survival are largely unexplored.Various idealized models, simplifying the swimming organisms to combinations of point forces acting on the water, have been used to describe the fluid disturbance generated by moving and feeding plankton. A self-propelled plankton is often described by a so-called stresslet (two oppositely directed point forces of equal magnitude), a hovering one by a stokeslet (a stationary point force), and a jumping animal by an impulsive stresslet (a stresslet working impulsively) (9, 11, 12). These highly idealized models yield very different predictions of the spatial attenuation of the fluid disturbance and, thus, of how far away the feeding and swimming animal can be detected. A few studies have compared observed flow patterns with those predicted from these simple models and in some cases found fair comparisons (4, 14–17). However, numerical simulations as well as observations of self-propelled microplankton have demonstrated that the distribution of propulsion forces, i.e., the position of flagella, cilia, or appendages on the (cell) body, may have a profound effect on the imposed fluid flow (18, 19). Also, most of the idealized models ignore the fact that swimming in most cases is unsteady, which leads to fluctuating flows at scales smaller than the Stokes length scale (ν/ω, where ν is the kinematic viscosity and ω is the beat frequency) (e.g., ref. 19). The simple, idealized models hitherto applied may be insufficient to represent the diverse propulsion modes observed in real organisms and to understand the associated trade-offs.Feeding and swimming are often part of the same process in zooplankton. Many zooplankton generate a feeding current that at the same time propels the animal through the water. In others, feeding and swimming are separate processes. For example, ambush feeding “sit-and-wait” zooplankters do not move as part of feeding but may swim to undertake vertical migration or to search for mates or patches of elevated food availability. Also, many of the plankton that generate a feeding current by vibrating appendages may in addition swim by using the same appendages in a different way (e.g., the nauplius larvae of most crustaceans) or by using other swimming appendages dedicated to propel themselves (most pelagic copepods and cladocerans).Whereas feeding and swimming may both compromise the survival of the organism, the trade-offs may be different. To get sufficient food, zooplankters need to daily clear a volume of water for prey that corresponds to about 10⁶ times their own body volume (20, 21) and hence, implicit in the feeding process is the need to examine or process large volumes of water. In contrast, dedicated swimming should translate the organism through the water as quietly as possible. Thus, we hypothesize that in microplankton, dedicated swimming produces flow fields that attenuate more readily and/or have a smaller spatial extension than the cases in which feeding and propulsion are intimately related.In this study we use particle image velocimetry (PIV) to describe the flow fields generated by micron- to millimeter-sized feeding and swimming zooplankton that use a variety of propulsion modes. We show that—across taxa and sizes—dedicated swimming produces flow fields with a much smaller spatial extension and a faster spatial attenuation than those produced by the plankton for which feeding and swimming are integrated, and we characterize the propulsion modes that minimize susceptibility to rheotactic predators.