Orosensory contributing compounds in crowberry (Empetrum nigrum)

原子吸收光谱英文Atomic Absorption Spectroscopy (AAS) is an analytical technique used to identify and quantify the presence of various metallic elements in a sample. This technique involves the use of specific wavelengths of light to determine the concentration of elements present in a sample.In AAS, a sample is atomized and converted into the gaseous state by heating it in a flame or furnace. The analyte atoms in the sample are then excited by exposure to radiation of a specific wavelength. At a certain wavelength, the atoms will absorb the radiation and move to a higher energy level. The amount of radiation absorbed by the analyte atoms is then detected and measured by a detector, which is usually a photomultiplier tube. The amount of radiation absorbed is directly proportional to the concentration of the analyte in the sample.AAS is particularly useful in the detection and quantification of heavy metals such as lead, mercury, and cadmium. These toxic elements can accumulate in human tissues and cause serious health problems, including cancer and neurological disorders. The accurate measurement of their presence in various environmental, biological, and industrial samples is, therefore, essential.One of the greatest advantages of AAS is its ability to detect trace amounts of elements in a sample. This is due to its high sensitivity, which can detect as little as parts per billion (ppb) of an element present in a sample. Another major advantage of AAS is its accuracy, which is crucial when determining the presence of potentially toxic elements in a sample.AAS is a complex analytical technique that requires careful sample preparation, calibration, and standardization. The accuracy and precision of this technique depend on several factors, including the quality of the sample, the choice of analytical wavelength, and the instrument calibration.In summary, Atomic Absorption Spectroscopy is a highly sensitive and accurate analytical technique for the detection and quantification of heavy metals and other metallic elements in a sample. Its potential applications are vast, ranging from environmental monitoring to biomedical research and food safety testing.。

Ecology is the scientific study of the interactions of organisms and their environment.The biosphere is the part of Earth where life exists.All organisms live and interact in the biosphere.To understand relationships in biosphere, ecologists study events and organisms that range in complexity from a single individual to the entire biosphereBiotic factors that are living things that influence other organisms in an ecosystem.Abiotic factors are physical or nonliving factors that shape and ecosytem.Ecologists study many levels of organization.• individual organisms• species—a group of similar organisms that breed and produce fertile offspring• population—a group of individuals of the same species that live in the same area• community—a collection of different populations that live together in an area• ecosystem—all organisms living in a specific place, together with their physical environment• biome—a group of ecosystems with the same climate and similar dominant communities• biosphere—the part of the planet (land, water, and air) where all life exists.Scientists conduct ecological research using three basic approaches: \1.observing,2.experimenting,3.modeling.All of these approaches rely on the application of scientific methods to guide ecological inquiry.∙Observing is often the first step in asking ecological questions.∙Observations can also be used when designing experiments and making models.∙Experiments can be used to test hypotheses.∙They may be done in a laboratory or in the field.∙Modeling helps scientists understand complex processes.3–2 Energy FlowOrganisms use energy from the environment for life processes.Living things get energy in different ways.Sunlight is the main energy source for life on Earth.anisms that use the energy in sunlight or chemicals to make food are called autotrophs.Autotrophs, also called producers, make food in two ways.1.Some autotrophs use light energy to make food in a process called photosynthesis.o In photosynthesis, carbon dioxide and water are changed to carbohydrates and oxygen.o Plants, some algae, and certain bacteria carry out photosynthesis.o Some types of organisms rely on the energy stored in organic chemical compounds.2.Some autotrophs use chemical energy to make carbohydrates is called chemosynthesis.o Only certain types of bacteria carry out chemosynthesis.Organisms that rely on other organisms for energy and food are called heterotrophs.Heterotrophs also are called consumers.Types of heterotrophs.o Herbivores, such as cows, get energy by eating only plants.o Carnivores, such as snakes, get energy by eating only animals.o Omnivores, such as humans, get energy by eating both plants and animals.o Detritivores, such as earthworms, feed on the remains (dead matter) or wastes of other organisms.o Insectivores –such a anteaters, or some birds.o Scavengers an organism that feeds on dead or once living organismso Decomposers, such as fungi, break down organic matter.Energy flows through an ecosystem in one direction.It flows from the sun (or inorganic compounds) to autotrophs and then to heterotrophs.A food chain shows how living things transfer energy by eating and being eaten.For ex. a food chain might consist of grass (producer), an antelope (herbivore), and a coyote (carnivore).A food web links together all of the food chains in an ecosystem.For example, rabbits may also feed on the grass in the food chain above. These rabbits may be eaten by the coyotes. The feeding relationships of the grass, rabbits, antelopes, and coyotes make up a food web.Each step in a food chain or food web is called a trophic level.o Producers are at the first trophic levelo Consumers make up higher trophic levels.o Each consumer depends on the trophic level below it for energy.Ecological pyramids are diagrams that show the relative amounts of energy or matter at each trophic level.Only about 10 percent of the energy available at one trophic level is passed on to organisms at the next trophic level.Three types of ecological pyramids are1.Energy pyramids show how much energy is available at each trophic level.2.Biomass pyramidsshow the biomass, or total amount of living tissue, at each trophiclevel.3.Pyramid of numbers shows the relative number of individual organisms at each trophiclevel.3–3 Cycles of MatterEnergy and matter move through the biosphere very differently.Unlike the one-way flow of energy, matter is recycled within and between ecosystems. Matter, including water and nutrients, moves through organisms and parts of the biosphere through BIOCHEMICAL CYCLES.The Water Cycle.o All living things need water to survive.o Water cycles between the ocean, atmosphere, land, and living things.o Many processes part of the water cycle. Ex. during evaporation liquid water changes to gas.o Transpiration is the evaporation of water from the leaves of plants.o Water changes from a gas to a liquid through the process of condensation.o Water vapor in the atmosphere condenses into tiny droplets that form clouds.o When the droplets get large enough, they fall to Earth’s surface as precipitation.Nutrients are chemical substances that organisms need to survive.Lliving organism needs nutrients to build tissues and carry out essential life functions. Like water, nutrients are passed between organisms and the environment through biogeochemical cycles.The Carbon Cycle.o Carbon is a key part of living tissue.o Photosynthesis and cellular respiration are parts of the carbon cycle.o Human activities such as burning fossil fuels are also parts of the carbon cycle.The Nitrogen Cycle.o Organisms need nitrogen to build proteins.o Different forms of nitrogen cycle through the biosphere.o Nitrogen gas is the most abundant form of nitrogen on Earth.o However, only certain kinds of bacteria can use this form directly.o These bacteria change nitrogen gas into ammonia in a process called nitrogen fixation.o Other bacteria in the soil convert ammonia into nitrates and nitrites.o When organisms die, decomposers return nitrogen to the soil.o Other bacteria change nitrogen compounds called nitrates back into nitrogen gas.o This process is called denitrification.The Phosphorus Cycle.o Most phosphorus is stored in rocks and ocean sediments.o This phosphorus is slowly released into water and soil and then used by organisms.o Phosphorus is a key part of DNA and RNA.Primary productivityo It is the rate at which producers form organic matter in an ecosystem.o The availability of a nutrient affects primary productivity of a producer.o A nutrient that is scarce or cycles slowly through an ecosystem is a limiting nutrient.o A limiting nutrient can affect ecosystem health.。

Biosensors and Bioelectronics Biosensors and bioelectronics have emerged as crucial technologies in thefield of medical diagnostics, environmental monitoring, and biotechnology. These innovative tools have the potential to revolutionize the way we detect and analyze biological molecules, offering faster, more sensitive, and more cost-effective solutions compared to traditional methods. The integration of biological components with electronic systems has paved the way for a wide range of applications, from glucose monitoring for diabetes management to the detection of pathogens in food and water. In this discussion, we will explore the significance of biosensors and bioelectronics, their current applications, and the future prospects of these technologies. One of the key advantages of biosensors and bioelectronics is their ability to provide real-time and on-site monitoring of various biological parameters. For instance, biosensors can be used tocontinuously monitor glucose levels in diabetic patients, allowing for timely adjustments in medication and diet. This not only improves the quality of life for the patients but also reduces the healthcare costs associated with managing diabetes. Similarly, bioelectronic devices can be employed for environmental monitoring, enabling the rapid detection of pollutants and toxins in air and water. This capability is invaluable for ensuring public health and safety, as well asfor regulatory compliance in industrial settings. Moreover, biosensors and bioelectronics offer enhanced sensitivity and specificity in detecting target analytes. By leveraging the unique recognition properties of biological molecules such as enzymes, antibodies, and nucleic acids, these technologies can achieve highly selective detection of specific compounds, including biomarkers fordiseases and environmental contaminants. This high level of specificity isessential for accurate diagnosis and monitoring, particularly in the context of complex biological samples where interference from other molecules is common. As a result, biosensors and bioelectronics have the potential to advance personalized medicine by enabling the detection of individual-specific biomarkers for early disease diagnosis and treatment optimization. In addition to their analytical capabilities, biosensors and bioelectronics are also driving innovations in the field of biotechnology. For example, these technologies are being utilized forhigh-throughput screening of drug candidates, rapid analysis of genetic variations, and monitoring of cellular activities. By interfacing biological systems with electronic transducers, researchers and industry professionals are able to gain deeper insights into the functioning of living organisms at the molecular level. This knowledge not only accelerates the development of novel therapeutics and diagnostics but also contributes to our fundamental understanding of biological processes. Looking ahead, the future of biosensors and bioelectronics holds tremendous promise for further advancements and applications. Ongoing research is focused on developing miniaturized and wearable biosensor devices that can seamlessly integrate into everyday life, enabling continuous health monitoring and early intervention. Furthermore, the convergence of biosensors with other emerging technologies such as artificial intelligence and nanotechnology is expected to unlock new possibilities in precision medicine, environmental surveillance, and bioprocessing. As these interdisciplinary collaborations continue to evolve, wecan anticipate the emergence of highly sophisticated bioelectronic systems with unprecedented capabilities. Despite the remarkable progress in biosensors and bioelectronics, there are still challenges that need to be addressed to fully realize their potential. One of the primary obstacles is the need for standardization and validation of these technologies to ensure their reliability and reproducibility across different settings. Additionally, there are concerns regarding the ethical implications of widespread biosensor deployment,particularly in terms of data privacy, consent, and equitable access to these advanced diagnostic tools. As these discussions unfold, it is essential for stakeholders from diverse fields including science, healthcare, ethics, andpolicy-making to collaborate and establish guidelines that uphold the responsible and equitable use of biosensors and bioelectronics. In conclusion, biosensors and bioelectronics represent a transformative force in the realms of healthcare, environmental monitoring, and biotechnology. Their ability to seamlessly interface biological recognition elements with electronic transducers has unlocked new possibilities for real-time, sensitive, and selective detection of a wide range of analytes. As these technologies continue to evolve and diversify, they hold the potential to revolutionize personalized medicine, environmental sustainability,and bioprocessing. However, it is imperative to address the technical, ethical, and regulatory challenges associated with biosensors and bioelectronics to ensure their responsible and equitable integration into society. By fostering interdisciplinary collaborations and engaging in thoughtful discourse, we can harness the full potential of biosensors and bioelectronics for the betterment of humanity.。

世界卫生组织国际癌症研究机构致癌物清单
1类致癌物清单（共120种）
1
2类致癌物清单（共380种，含2A类81种，2B类299种）
2A类致癌物：对人很可能致癌，此类致癌物对人致癌性证据有限，对实验动物致癌性证据充分。

2B类致癌物：对人可能致癌，此类致癌物对人致癌性证据有限，对实验动物致癌性证据并不充分；或对人类致癌性证据不足，对实验动物致癌性证据充分。

3类致癌物清单（共502种）3
4类致癌物清单（1种）
备注：上述清单是中国食品药品检定研究院安全评价研究所根据世界卫生组织国际癌症研究机构2017年10月27日公布的致癌物清单进行的初步整理，仅供参考。

Adopted:3 October 2008© OECD, (2008) You are free to use this material for personal, non-commercial purposes without seeking prior consent from the OECD, provided the source is duly mentioned. Any commercial use of this material is subject to written permission from the OECD.OECD GUIDELINES FOR THE TESTING OF CHEMICALSRepeated Dose 28-Day Oral Toxicity Study in RodentsINTRODUCTION1 OECD Guidelines for the Testing of Chemicals are periodically reviewed in the light of scientific progress. The original Test Guideline 407 was adopted in 1981. In 1995 a revised version was adopted, to obtain additional information from the animal used in the study, in particular on neurotoxicity and immunotoxicity.2 In 1998, the OECD initiated a high-priority activity, to revise existing Test Guidelines and to develop new Test Guidelines for the screening and testing of potential endocrine disruptors (8). One element of the activity was to update the existing OECD guideline for “repeated dose 28-day oral toxicity study in rodents” (TG 407) by parameters suitable to detect endocrine activity of test substances. This procedure underwent an extensive international program to test for the relevance and practicability of the additional parameters, the performance of these parameters for chemicals with (anti)oestrogenic, (anti)androgenic, and (anti)thyroid activity, the intra- and interlaboratory reproducibility, and the interference of the new parameters with those required by the prior TG 407. The large amount of data thereby obtained has been compiled and evaluated in detail in a comprehensive OECD report (9). This updated Test Guideline 407 is the outcome of the experience and results gained during the international test program. This TG 407 allows certain endocrine mediated effects to be put into context with other toxicological effects.INITIAL CONSIDERATIONS AND LIMITATIONS3 In the assessment and evaluation of the toxic characteristics of a chemical, the determination of oral toxicity using repeated doses may be carried out after initial information on toxicity has been obtained by acute toxicity testing. This TG is intended to investigate effects on a very broad variety of potential targets of toxicity. It provides information on the possible health hazards likely to arise from repeated exposure over a relatively limited period of time, including effects on the nervous, immune and endocrine systems. Regarding these particular endpoints, it should identify chemicals with neurotoxic potential, which may warrant further in-depth investigation of this aspect, and chemicals that interfere with thyroid physiology. It may also provide data on chemicals that affect the male and/or female reproductive organs in young adult animals and may give an indication of immunological effects.4 The results from the TG 407 should be used for hazard identification and risk assessment. The results obtained by the endocrine related parameters should be seen in the context of the “OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupting Chemicals” (11). The method comprises the basic repeated dose toxicity study that may be used for chemicals on which a 90-day study is not warranted (e.g. when the production volume does not exceed certain limits) or as a preliminary to a long-term study. The duration of exposure should be 28 days.5 The international program conducted on the validation of parameters suitable to potentially detect endocrine activity of test substance showed that the quality of data obtained by this TG 407 will depend much on the experience of the test laboratory. This relates specifically to the histopathological determination of cyclic changes in the female reproductive organs and to the weight determination of thesmall hormone dependent organs which are difficult to dissect. A guidance on histopathology has been developed (19). It is available on the OECD public website on Test Guidelines. It is intended to assist pathologists in their examinations and help increase the sensitivity of the assay. A variety of parameters were found to be indicative of endocrine-related toxicity and have been incorporated in the TG. Parameters for which insufficient data were available to prove usefulness or which showed only weak evidence in the validation programme of their ability to help in detection of endocrine disrupters are proposed as optional endpoints (see Annex 2).6 On the basis of data generated in the validation process, it must be emphasized that the sensitivity of this assay is not sufficient to identify all substances with (anti)androgenic or (anti)oestrogenic modes of action (9). The TG is not performed in a life-stage that is most sensitive to endocrine disruption. The TG nevertheless, during the validation process identified compounds weakly and strongly affecting thyroid function, and strong and moderate endocrine active substances acting through oestrogen or androgen receptors, but in most cases failed to identify endocrine active substances that weakly affect oestrogen or androgen receptors. Thus it can’t be described as a screening assay for endocrine activity.7 Consequently, the lack of effects related to these modes of action can not be taken as evidence for the lack of effects on the endocrine system. Regarding endocrine mediated effects, compound characterization should not therefore be based on the results of this TG alone but should be used in a weight of evidence approach incorporating all existing data on a chemical to characterise potential endocrine activity. For this reason, regulatory decision making on endocrine activity (compound characterisation) should be a broadly based approach, not solely reliant on results from application of this TG.8 It is acknowledged that all animal-based procedures will conform to local standards of animal care; the descriptions of care and treatment set forth below are minimal performance standards, and will be superseded by local regulations where more stringent. Further guidance of the humane treatment of animals is given by the OECD(14).9 Definitions used are given in Annex 1.PRINCIPLE OF THE TEST10 The test substance is orally administered daily in graduated doses to several groups of experimental animals, one dose level per group for a period of 28 days. During the period of administration the animals are observed closely, each day for signs of toxicity. Animals that die or are euthanised during the test are necropsied and at the conclusion of the test surviving animals are euthanised and necropsied. A 28 day study provides information on the effects of repeated oral exposure and can indicate the need for further longer term studies. It can also provide information on the selection of concentrations for longer term studies. The data derived from using the TG should allow for the characterization of the test substance toxicity, for an indication of the dose response relationship and the determination of the No-Observed Adverse Effect Level (NOAEL).DESCRIPTION OF THE METHODSelection of animal species11 The preferred rodent species is the rat, although other rodent species may be used. If the parameters specified within this TG 407 are investigated in another rodent species a detailed justification should be given. Although it is biologically plausible that other species should respond to toxicants in a similar manner to the rat, the use of smaller species may result in increased variability due to technical © OECD, (2008) 2challenges of dissecting smaller organs. In the international validation program for the detection of endocrine disrupters, the rat was the only species used. Young healthy adult animals of commonly used laboratory strains should be employed. Females should be nulliparous and non pregnant. Dosing should begin as soon as feasible after weaning, and, in any case, before the animals are nine weeks old. At the commencement of the study the weight variation of animals used should be minimal and not exceed ± 20% of the mean weight of each sex. When a repeated oral dose is conducted as a preliminary to a longer-term study, it is preferrable that animals from the same strain and source should be used in both studies. Housing and feeding12 All procedures should conform to local standards of laboratory animal care. The temperature in the experimental animal room should be 22°C (± 3°C). Although the relative humidity should be at least 30% and preferably not to exceed 70% other than during room cleaning, the aim should be 50-60%. Lighting should be artificial, the photoperiod being 12 hours light, 12 hours dark. For feeding, conventional laboratory diets may be used with an unlimited supply of drinking water. The choice of diet may be influenced by the need to ensure a suitable admixture of a test substance when administered by this method. Animals should be group housed in small groups of the same sex; animals may be housed individually if scientifically justified. For group caging, no more than five animals should be housed per cage.13 The feed should be regularly analysed for contaminants. A sample of the diet should be retained until finalisation of the report.Preparation of animals14 Healthy young adult animals are randomly assigned to the control and treatment groups. Cages should be arranged in such a way that possible effects due to cage placement are minimized. The animals are identified uniquely and kept in their cages for at least five days prior to the start of the treatment study to allow for acclimatisation to the laboratory conditions.Preparation of doses15 The test compound is administered by gavage or via the diet or drinking water. The method of oral administration is dependent on the purpose of the study, and the physical/chemical/toxico-kinetic properties of the test material.16 Where necessary, the test substance is dissolved or suspended in a suitable vehicle. It is recommended that, wherever possible, the use of an aqueous solution/suspension be considered first, followed by consideration of a solution/suspension in oil (e.g. corn oil) and then by possible solution in other vehicles. For vehicles other than water the toxic characteristics of the vehicle must be known. The stability of the test substance in the vehicle should be determined.PROCEDURENumber and sex of animals17 At least 10 animals (five female and five male) should be used at each dose level. If interim euthanasia are planned, the number should be increased by the number of animals scheduled to be euthanised before the completion of the study. Consideration should be given to an additional satellite group of ten animals (five per sex) in the control and in the top dose group for observation of reversibility, persistence, or delayed occurrence of toxic effects, for at least 14 days post treatment.3 © OECD, (2008)Dosage18 Generally, at least three test groups and a control group should be used, but if from assessment of other data, no effects would be expected at a dose of 1000mg/kg bw/d, a limit test may be performed. If there are no suitable data available, a range finding study (animals of the same strain and source) may be performed to aid the determination of the doses to be used. Except for treatment with the test substance, animals in the control group should be handled in an identical manner to the test group subjects. If a vehicle is used in administering the test substance, the control group should receive the vehicle in the highest volume used.19 Dose levels should be selected taking into account any existing toxicity and (toxico-) kinetic data available for the test compound or related materials. The highest dose level should be chosen with the aim of inducing toxic effects but not death or severe suffering. Thereafter, a descending sequence of dose levels should be selected with a view to demonstrating any dosage related response and no-observed-adverse effects at the lowest dose level (NOAEL). Two to four fold intervals are frequently optimal for setting the descending dose levels and addition of a fourth test group is often preferable to using very large intervals (e.g. more than a factor of 10) between dosages.20 In the presence of observed general toxicity (e.g. reduced body weight, liver , heart, lung or kidney effects, etc.) or other changes that may not be toxic responses (e.g. reduced food intake, liver enlargement), observed effects on immune, neurological or endocrine sensitive endpoints should be interpreted with caution.Limit test21 If a test at one dose level of at least 1000 mg/kg body weight/day or, for dietary or drinking water administration, an equivalent percentage in the diet, or drinking water (based upon body weight determinations), using the procedures described for this study, produces no observable toxic effects and if toxicity would not be expected based upon data from structurally related compounds, then a full study using three dose levels may not be considered necessary. The limit test applies except when human exposure indicates the need for a higher dose level to be used.Administration of doses22 The animals are dosed with test substance daily 7 days each week for a period of 28 days. When the test substance is administered by gavage, this should be done in a single dose to the animals using a stomach tube or a suitable intubation cannula. The maximum volume of liquid that can be administered at one time depends on the size of the test animal. The volume should not exceed 1 ml/100g body weight except in the case of aqueous solutions where 2 ml/100 g body weight may be used. Except for irritating or corrosive substances, which will normally reveal exacerbated effects with higher concentrations, variability in test volume should be minimized by adjusting the concentration to ensure a constant volume at all dose levels.23 For substances administered via the diet or drinking water it is important to ensure that the quantities of the test substance involved do not interfere with normal nutrition or water balance. When the test substance is administered in the diet either a constant dietary concentration (ppm) or a constant dose level in terms of the animals' body weight may be used; the alternative used must be specified. For a substance administered by gavage, the dose should be given at similar times each day, and adjusted as necessary to maintain a constant dose level in terms of animal body weight. Where a repeated dose study is used as a preliminary to a long term study, a similar diet should be used in both studies.© OECD, (2008) 4Observations24 The observation period should be 28 days. Animals in a satellite group scheduled for follow-up observations should be kept for at least 14 days without treatment to detect delayed occurrence, or persistence of, or recovery from toxic effects.25 General clinical observations should be made at least once a day, preferably at the same time(s) each day and considering the peak period of anticipated effects after dosing. The health condition of the animals should be recorded. At least twice daily, all animals are observed for morbidity and mortality.26 Once before the first exposure (to allow for within-subject comparisons), and at least once a week thereafter, detailed clinical observations should be made in all animals. These observations should be made outside the home cage in a standard arena and preferably at the same time of day on each occasion. They should be carefully recorded, preferably using scoring systems, explicitly defined by the testing laboratory. Effort should be made to ensure that variations in the test conditions are minimal and that observations are preferably conducted by observers unaware of the treatment. Signs noted should include, but not be limited to, changes in skin, fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g. lacrimation, piloerection, pupil size, unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypies (e.g. excessive grooming, repetitive circling) or bizarre behaviour (e.g. self-mutilation, walking backwards) should also be recorded (2).27 In the fourth exposure week sensory reactivity to stimuli of different types (2) (e.g. auditory, visual and proprioceptive stimuli) (3)(4)(5), assessment of grip strength (6) and motor activity assessment (7) should be conducted. Further details of the procedures that could be followed are given in the respective references. However, alternative procedures than those referenced could be used.28 Functional observations conducted in the fourth exposure week may be omitted when the study is conducted as a preliminary study to a subsequent subchronic (90-day) study. In that case, the functional observations should be included in this follow-up study. On the other hand, the availability of data on functional observations from the repeated dose study may enhance the ability to select dose levels for a subsequent subchronic study.29 As an exception, functional observations may also be omitted for groups that otherwise reveal signs of toxicity to an extent that would significantly interfere with the functional test performance.30 At necropsy, the oestrus cycle of all females could be determined (optional) by taking vaginal smears. These observations will provide information regarding the stage of oestrus cycle at the time of sacrifice and assist in histological evaluation of estrogen sensitive tissues (see guidance on histopathology (19)).Body weight and food/water consumption31 All animals should be weighed at least once a week. Measurements of food consumption should be made at least weekly. If the test substance is administered via the drinking water, water consumption should also be measured at least weekly.5 © OECD, (2008)© OECD, (2008) 6 Haematology32 The following haematological examinations should be made at the end of the test period: haematocrit, haemoglobin concentrations, erythrocyte count, reticulocytes, total and differential leucocyte count, platelet count and a measure of blood clotting time/potential. Other determinations that should be carried out, if the test substance or its putative metabolites have or are suspected to have oxidising properties include methaemoglobin concentration and Heinz bodies.33 Blood samples should be taken from a named site just prior to or as part of the procedure for euthanasia of the animals, and stored under appropriate conditions. Animals should be fasted overnight prior to euthanasia 1– time of sacrifice because of diurnal variation of hormone concentrations.Clinical biochemistry34 Clinical biochemistry determinations to investigate major toxic effects in tissues and, specifically, effects on kidney and liver, should be performed on blood samples obtained of all animals just prior to or as part of the procedure for euthanasia of the animals (apart from those found moribund and/or euthanised prior to the termination of the study). Investigations of plasma or serum shall include sodium, potassium, glucose, total cholesterol, urea, creatinine, total protein and albumin, at least two enzymes indicative of hepatocellular effects (such as alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl trans-peptidase and glutamate dehydrogenase), and bile acids. Measurements of additional enzymes (of hepatic or other origin) and bilirubin may provide useful information under certain circumstances.35 Optionally, the following urinalysis determinations could be performed during the last week of the study using timed urine volume collection; appearance, volume, osmolality or specific gravity, pH, protein, glucose and blood/blood cells.36 In addition, studies to investigate plasma or serum markers of general tissue damage should be considered. Other determinations that should be carried out, if the known properties of the test substance may, or are suspected to, affect related metabolic profiles include calcium, phosphate, triglycerides, specific hormones, and cholinesterase. These need to be identified for chemicals in certain classes or on a case-by-case basis.37 Although in the international evaluation of the endocrine related endpoints a clear advantage for the determination of thyroid hormones (T3, T4) and TSH could not be demonstrated, it may be helpful to retain plasma or serum samples to measure T3, T4 and TSH (optional) if there is an indication for an effect on the pituitary-thyroid axis. These samples may be frozen at -20° for storage. The following factors may influence the variability and the absolute concentrations of the hormone determinations:– method of sacrifice to avoid undue stress to the animals that may affect hormone concentrations – test kits for hormone determinations that may differ by their standard curves.1 For a number of measurements in serum and plasma, most notably for glucose, overnight fasting would be preferable. The major reason for this preference is that the increased variability which would inevitably result from non-fasting, would tend to mask more subtle effects and make interpretation difficult. On the other hand, however, overnight fasting may interfere with the general metabolism of the animals and, particularly in feeding studies, may disturb the daily exposure to the test substance. If overnight fasting is adopted, clinical biochemical determinations should be performed after the conduct of functional observations in week 4 of the study.Definitive identification of thyroid-active chemicals is more reliable by histopathological analysis rather than hormone levels.38 Plasma samples specifically intended for hormone determination should be obtained at a comparable time of the day. It is recommended that consideration should be given to T3, T4 and TSH determinations triggered based upon alterations of thyroid histopathology. The numerical values obtained when analysing hormone concentrations differ with various commercial assay kits. Consequently, it may not be possible to provide performance criteria based upon uniform historical data. Alternatively, laboratories should strive to keep control coefficients of variation below 25 for T3 and T4 and below 35 for TSH. All concentrations are to be recorded in ng/ml.39 If historical baseline data are inadequate, consideration should be given to determination of haematological and clinical biochemistry variables before dosing commences or preferably in a set of animals not included in the experimental groups.PATHOLOGYGross necropsy40 All animals in the study shall be subjected to a full, detailed gross necropsy which includes careful examination of the external surface of the body, all orifices, and the cranial, thoracic and abdominal cavities and their contents. The liver, kidneys, adrenals, testes, epididymides, prostate + seminal vesicles with coagulating glands as a whole, thymus, spleen, brain and heart of all animals (apart from those found moribund and/or euthanised prior to the termination of the study) should be trimmed of any adherent tissue, as appropriate, and their wet weight taken as soon as possible after dissection to avoid drying. Care must be exercised when trimming the prostate complex to avoid puncture of the fluid filled seminal vesicles. Alternatively, seminal vesicles and prostate may be trimmed and weighed after fixation.41 In addition, two other tissues could be optionally weighed as soon as possible after dissection, to avoid drying: paired ovaries (wet weight) and uterus, including cervix (guidance on removal and preparation of the uterine tissues for weight measurement is provided in TG 440 (18)).42 The thyroid weight (optional) could be determined after fixation. Trimming should also be done very carefully and only after fixation to avoid tissue damage. Tissue damage could compromise histopathology analysis.43 The following tissues should be preserved in the most appropriate fixation medium for both the type of tissue and the intended subsequent histopathological examination (see paragraph 47): all gross lesions, brain (representative regions including cerebrum, cerebellum and pons), spinal cord, eye, stomach, small and large intestines (including Peyer's patches), liver, kidneys, adrenals, spleen, heart, thymus, thyroid, trachea and lungs (preserved by inflation with fixative and then immersion), gonads (testis and ovaries), accessory sex organs ( uterus and cervix, epididymides, prostate + seminal vesicles with coagulating glands), vagina, urinary bladder, lymph nodes (besides the most proximal draining node another lymph node should be taken according to the laboratory’s experience (15)), peripheral nerve (sciatic or tibial) preferably in close proximity to the muscle, skeletal muscle and bone, with bone marrow (section or, alternatively, a fresh mounted bone marrow aspirate). It is recommended that testes be fixed by immersion in Bouin’s or modified Davidson’s fixative (16) (17). The tunica albuginea must be gently and shallowly punctured at the both poles of the organ with a needle to permit rapid penetration of the fixative. The clinical and other findings may suggest the need to examine additional tissues. Also any organs considered likely to be target organs based on the known properties of the test substance should be preserved.7 © OECD, (2008)44 The following tissues may give valuable indication for endocrine-related effects: Gonads (ovaries and testes), accessory sex organs (uterus including cervix, epididymides, seminal vesicles with coagulation glands, dorsolateral and ventral prostate), vagina, pituitary, male mammary gland, the thyroid and adrenal gland. Changes in male mammary glands have not been sufficiently documented but this parameter may be very sensitive to substances with estrogenic action. Observation of organs/tissues that are not listed in paragraph 43 is optional (see Annex 2).45 The Guidance on histopathology (19) details extra information on dissection, fixation, sectioning and histopathology of endocrine tissues.46 In the international test program some evidence was obtained that subtle endocrine effects by chemicals with a low potency for affecting sex hormone homeostasis may be identified by disturbance of the synchronisation of the oestrus cycle in different tissues and not so much by frank histopathological alterations in female sex organs. Although no definitive proof was obtained for such effects, it is recommended that evidence of possible asynchrony of the oestrus cycle should be taken into account in interpretation of the histopathology of the ovaries (follicular, thecal, and granulosa cells), uterus, cervix and vagina. If assessed, the stage of cycle as determined by vaginal smears could be included in this comparison as well.Histopathology47 Full histopathology should be carried out on the preserved organs and tissues of all animals in the control and high dose groups. These examinations should be extended to animals of all other dosage groups, if treatment-related changes are observed in the high dose group.48 All gross lesions shall be examined.49 When a satellite group is used, histopathology should be performed on tissues and organs identified as showing effects in the treated groups.DATA AND REPORTINGData50 Individual data should be provided. Additionally, all data should be summarised in tabular form showing for each test group the number of animals at the start of the test, the number of animalsfound dead during the test or euthanised for humane reasons and the time of any death or euthanasia, the number showing signs of toxicity, a description of the signs of toxicity observed, including time of onset, duration, and severity of any toxic effects, the number of animals showing lesions, the type of lesions, their severity and the percentage of animals displaying each type of lesion.51 When possible, numerical results should be evaluated by an appropriate and generally acceptable statistical method. Comparisons of the effect along a dose range should avoid the use of multiple t-tests. The statistical methods should be selected during the design of the study.52 For quality control it is proposed that historical control data are collected and that for numerical data coefficients of variation are calculated, especially for the parameters linked with endocrine disrupter detection. These data can be used for comparison purposes when actual studies are evaluated.© OECD, (2008)8。

江福林，卢云浩，何强. 茶多酚对植物乳杆菌、金黄色葡萄球菌和大肠杆菌生长的双向调节作用[J]. 食品工业科技，2023，44（22）：152−159. doi: 10.13386/j.issn1002-0306.2023040081JIANG Fulin, LU Yunhao, HE Qiang. Dual-directional Regulation of Tea Polyphenols on the Growth of Lactobacillus plantarum ,Staphylococcus aureus , and Escherichia coli [J]. Science and Technology of Food Industry, 2023, 44(22): 152−159. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023040081· 生物工程 ·茶多酚对植物乳杆菌、金黄色葡萄球菌和大肠杆菌生长的双向调节作用江福林1，卢云浩2，何　强1,*（1.四川大学轻工科学与工程学院，四川成都 610065；2.成都大学食品与生物工程学院，四川成都 610106）摘　要：增强益生菌产品中益生菌的活力，同时抑制食源性致病菌及腐败菌的生长能够提升产品品质稳定性。

在单培养及共培养条件下，采用传统计数法和高通量测序比较研究了不同浓度的茶多酚对益生菌植物乳杆菌、致病菌金黄色葡萄球菌和大肠杆菌生长的影响。

单培养结果显示，随着茶多酚浓度增加，植物乳杆菌活菌数先增加后降低，在浓度为2.0 mg/mL 时活菌数最多，而两株致病菌的存活率不断降低，其中金黄色葡萄球菌更为明显。

在共培养体系中（金黄色葡萄球菌/大肠杆菌-植物乳杆菌），随着培养时间延长，植物乳杆菌的生物量不断增加，而致病菌数量和培养基pH 不断降低。

气作用的食物，如槟榔、生萝卜等。

在起居方面，阳虚 质，平时注意保暖，避风寒。

气虚质，避免过度劳累，避 免重体力劳动或剧烈运动，防止汗出受凉，此外，可行柔和运动，如太极拳，加强盆底肌肉训练。

再者对于慢 性咳嗽及长期便秘患者，应及时治疗，以期全方位防治SUI 疾病，提高患者的生活质量。

参考文献[1 ]刘鸿雁，徐英敏，蒋士卿•妇科常见疾病的体质辨证与治疗[J].中国中医基础医学杂志,2011,17(8) =875-876.[2 ]杜彦芳，蒋妍，黄向华.女性尿失禁的分类及诊断标准[S].实用妇产科杂志,2018,34(3) ：164-167.[3 ]罗德毅，沈宏.女性尿失禁的诊断与鉴别诊断[J].中国实用妇科与产科杂志,2017 ,33(10) ：1002-1005.[4 ]中华医学会妇产科学分会妇科盆底学组.女性压力性尿失禁诊断和治疗指南(2017) [SJ.中华妇产科杂志,2017,52 ( 5 )：289-293.[5 ]孙咏，盛卫平.女性尿失禁的流行病学研究和防治[J]・中国医药指南,2010,8( 13):208-210.[6 ]王建业，钟晨阳.老年尿失禁的病因和治疗[J].中国实用内科杂志,2011 ,31(1) :25-27.[7 ]王莎，邓琛.女性尿失禁生活质量测评量表的研究进展[J] •中国全科医学,2017,20(23) ：2934-2938.[8 ]蔡舒，刘雪琴，李江婷.社区老年女性尿失禁患者抑郁状况的调査分析[J].护士进修杂志,2007 ,22(3) :274-276.[9 ]张萍华，张桂青，鲁谨•癌症病人抑郁的心理干预研究[J].全科护理 2OO9,7(1C) ：204-207.[10] 张蕾，杨颐，刘慧林，等.古代中医文献对于尿失禁的认识和治疗述要[J].中医文献杂志,2013,31(2) :54-56.[11] 孙维宁，王轶蓉.绝经过渡期压力性尿失禁中医治疗概况[J]. 云南中医中药杂志,2019,40(2) :70-72.[12] 薛丽飞.老年抑郁症证候与中医体质相关性研究[D].广州：广州中医药大学，2011.[13] 王琦.中医体质学说研究现状与展望[J].中国中医基础医学杂志,2002,8(2) ：6-15.[14] 高艳梅.太原地区女性压力性尿失禁发病相关因素及中医体质 类型研究[D].太原：山西中医药大学,2017.[15] 蔡东滨.抑郁焦虑障碍与中医体质的相关性研究[D].广州：广州中医药大学,2018.(本文校对：庄良武 收稿日期=2020 -04 - 17)醒脑开窍针法结合毫火针治疗梅杰综合征吴秋汶宋洪堰苏涛刘欢摘要：梅杰综合征是一种肌张力障碍性疾病，主要表现为双眼睑痉挛、面部肌张力障碍样不自主运动，又称眼睑痉挛•口下颌肌张力障碍。

Curiosity is a rover designed by NASA to explore the Gale Crater on Mars,which is believed to be the source of a vast lake that once existed on the planet.This mission aims to investigate the planets climate and geology,as well as search for signs of ancient life.Launched in November2011,Curiosity landed on Mars in August2012.It is equipped with a variety of scientific instruments to study the Martian surface and atmosphere.One of its key instruments is the Mars Hand Lens Imager MAHLI,which captures highresolution images of the rovers surroundings.The rover has discovered evidence of an ancient riverbed and lakebed,suggesting that Mars once had liquid water.This is significant because water is considered a key ingredient for life.Curiosity has also found organic molecules,which are the building blocks of life,in Martian rocks.Curiosity has also measured the Martian atmosphere and found it to be composed mainly of carbon dioxide,with traces of other gases.The rover has also detected methane,a gas that can be produced by geological or biological processes.In addition to its scientific mission,Curiosity has also captured stunning images of the Martian landscape.The rover has sent back panoramic views of the Gale Crater,showing its rugged terrain and the towering Mount Sharp in the distance.Despite facing technical challenges and harsh conditions on Mars,Curiosity has exceeded its expected lifespan and continues to explore the Red Planet.It has provided valuable insights into Mars past and present,and has inspired further exploration of our neighboring planet.In conclusion,the Curiosity rovers mission to explore the source of Mars ancient lake has been a remarkable success.It has expanded our understanding of the planets history and potential for life,and has paved the way for future Mars missions.。