2015 年江苏省药品注册分析报告

江苏省药物研发势头强劲，药品注册申报量连年位居全国首位。重点分析2015 年及“十二五”期间江苏省药品注册情况，并提 出进一步完善我省药品注册管理工作的措施。     

Phenoloxidase: a key component of the insect immune system

The innate immune system in insects is composed of a large variety of specific and non‐specific responses that are activated in response to the presence of foreign agents. One important element in such responses is the enzyme phenoloxidase (PO). Here, we review recent progress in PO research and discuss new applications in the emerging field of ecological immunology. Phenoloxidase produces indole groups, which are subsequently polymerized to melanin. The enzymatic reactions in turn produce a set of intermediate products such as quinones, diphenols, superoxide, hydrogen peroxide, and reactive nitrogen intermediates, which are important during defense against bacterial (gram+ and ?), fungal, and viral agents. Phenoloxidase requires a complex system of activation and inhibition that involves various cell types, PO zymogens, inhibitor enzymes, and signaling molecules. Finally, research in evolutionary ecology has studied the costs of PO in terms of resource use and pleiotropic relations with other key traits and functions. These studies indicate that PO is a costly trait, whose production and maintenance have fitness costs for hosts. Phenoloxidase does not seem to be an indicator of resistance but rather of host condition. Finally, we put forward some basic directions for future investigation of PO aimed at explaining its activating system, its substrates, its coordination with other immune components to fight off pathogens, and variation in PO in relation to gender, life stages, seasonality, and across different host species.     

Biomanipulation: retrospective and future development

Contaminants discharged to an estuary usually become associated with the near surface brackish waters and on an ebb tide these waters form a plume which streams away from the estuary mouth. As the plume mixes downwards, a localised region of minimum dilution may form at the sea-bed, depending on the rates of transverse and vertical mixing.A modelling study of the outflow from the Tees estuary suggests that regions of minimum dilution at the sea-bed could occur between 1.5 and 4.0 km from the estuary mouth, the latter corresponding to a tide of spring range. An estimate for the Humber outflow on a spring tide indicates that a similar impact region could occur at a distance of some 9 km from the entrance to the estuary. At the Tyne and Wear estuaries, the vertical mixing of contaminants is likely to be too slow for the regions of minimum dilution to form before the discharge plumes are cut off from the estuary mouths by the reversal of tidal flow.     

A Quality Control System Involving Peer Review of Abnormal Cervical Smears

An internal quality control system which is used in the centralized cytology laboratory of a population-based cervical cancer screening programme in Florence is described. It includes a peer review procedure. Abnormal cervical smears are circulated among all the cytologists and a consensus on the final diagnosis is reached. This daily procedure is designed to evaluate the performance of each cytologist and of the laboratory as a whole but can also be considered a valuable training opportunity. During an 18-month period 1197 smears were reviewed by 15 readers using a reporting form with six main categories of reporting (from ‘regative’ to ‘invasive carcinoma’), plus an ‘unsatisfactory’ category. Overall the concordance between the 15 cytologists, assessed using the kappa statistic (range 0.46–0.71; median 0.60), was good. the level of agreement increased when a weighted kappa statistic (range 0.55–0.78; median 0.68) was used. Kappa values were also calculated for specific categories and suggested an increasing concordance with increasing severity of the lesions, the categories of ‘severe dysplasia’ and ‘invasive carcinoma’ showing the highest agreement. the poor results for the ‘moderate dysplasia’ confirmed the need for combining this group with the ‘severe dysplasia’, as proposed in the Bethesda system.     

Commercially available luminometers and imaging devices for low-light level measurements and kits and reagents utilizing bioluminescence or chemiluminescence: Survey update 2

This survey was completed in December 1993 and includes products not covered in the luminometer survey (Jan 1992: Stanley PE, J Biolumin Chemilumin 1992; 7:77–108 and 7:157–69), kits and reagent survey (Nov 1992: Stanley PE, J Biolumin Chemilumin 1993; 8:51–63), update 1 (June 1993, luminometers, kits and reagents, Stanley PE, J Biolumin Chemilumin 1993; 8:237–40). Technical details are provided together with company address and contact information.     

Peptoids as tools and sensors

A review of molecular tools and sensors assembled on N-substituted glycine, or α-peptoid, oligomers between 2013 and November 2018 with the following sections: (a) Peptoids as crystal growth modifiers, (b) Peptoids as catalysts, (c) Ion and molecule sequestration and transport, (d) Peptoid sensors, (e) Macromolecule recognition, (f) Cellular transporters, (g) Medical imaging, (h) Future direction and (i) Summary and outlook. Peptoids are a promising class of peptide mimic making them an excellent platform for functional molecule preparation. Attributes of peptoid oligomers include: (a) the ease of precise sequence definition and mono-dispersity; (b) access to a vast chemical space within simple and repeating chemical preparative steps and (c) thermal, chemical and biological stability all lending support for their application in a number of areas, with some that have been realised to date. The peptoid tool and sensor examples selected have realised practical utility. They serve to illustrate the rapidity of new insight that can generate in many disparate areas of science and technology, enabling the quick assembly of design criteria for efficient peptoid molecular tools and sensors.     

Epilogue – one hundred years of nemertean research: Bürger (1895) to the present

The past one hundred years of research on nemerteansis reviewed. Scientific methodology and philosophyhave advanced considerably during this period, yetnemerteans remain one of the least well known ofinvertebrate groups; nemerteans are not just membersof a minor phylum, they constitute a neglected yethighly successful assemblage of animals. Despite manyworkers in the last hundred years having madesignificant contributions to our knowledge about thisphylum of worms, many aspects of their biology arestill virtually, if not totally, unknown, and theenormous advances in many areas of scientificknowledge have not been paralleled by comparable gainsin our understanding of nemerteans.     

Review of Information Resources to Support Human Exposure Assessment Models

Efforts to model human exposures to chemicals are growing more sophisticated and encompass increasingly complex exposure scenarios. The scope of such analyses has increased, growing from assessments of single exposure pathways to complex evaluations of aggregate or cumulative chemical exposures occurring within a variety of settings and scenarios. In addition, quantitative modeling techniques have evolved from simple deterministic analyses using single point estimates for each necessary input parameter to more detailed probabilistic analyses that can accommodate distributions of input parameters and assessment results. As part of an overall effort to guide development of a comprehensive framework for modeling human exposures to chemicals, available information resources needed to derive input parameters for human exposure assessment models were compiled and critically reviewed. Ongoing research in the area of exposure assessment parameters was also identified. The results of these efforts are summarized and other relevant information that will be needed to apply the available data in a comprehensive exposure model is discussed. Critical data gaps in the available information are also identified. Exposure assessment modeling and associated research would benefit from the collection of additional data as well as by enhancing the accessibility of existing and evolving information resources.