47 results about "Experimental Animal Models" patented technology

The invention discloses a construction method and application of a caenorhabditis elegans inflammation model, belongs to the technical field of model biology, and provides a construction method of a caenorhabditis elegans inflammation model, which comprises the following steps: putting L1-stage caenorhabditis elegans into a lipopolysaccharide solution, and carrying out induced culture to obtain induced cultured caenorhabditis elegans; placing the caenorhabditis elegans in a chromosome system, performing staining culture and centrifugation to obtain dyed caenorhabditis elegans, and placing the dyed caenorhabditis elegans on a culture medium for recovery to obtain the caenorhabditis The surface of the caenorhabditis elegans is provided with a transparent cuticle anatomical structure, the intestinal barrier damage condition is easy to observe after the intestinal tract is dyed by a dye, and the cell proliferation, tissue development and tissue integrity of the caenorhabditis elegans are easy to carry out fluorescence microscope and morphological analysis. A caenorhabditis elegans inflammation model is constructed through lipopolysaccharide induction, and a new experimental animal model is provided for screening anti-inflammatory drugs.

The invention relates to the technical field of disease animal models, in particular to a construction method, an evaluation method and application of a bipolar affective disorder liver stagnation and spleen deficiency syndrome combined animal model. According to the method, a liver depression and spleen deficiency syndrome modeling method is adopted for model construction, evaluation indexes are formulated by combining manic and depression behavior expressions of mice and innovatively combining typical expressions of liver depression and spleen deficiency, a liver depression and spleen deficiency syndrome animal model evaluation method is explored, and a thought is provided for achieving standardization and normalization of liver depression and spleen deficiency syndrome model evaluation. The modeling method is simple and economical, provides an experimental animal model for syndrome differentiation treatment of diseases, particularly provides a corresponding animal model for traditional Chinese medicine syndrome differentiation treatment and new drug pharmacological experiments, accelerates the progress of traditional Chinese medicine disease syndrome research and new drug development, provides technical service for drug evaluation, and has great application value.

The invention relates to the field of medical biology, and discloses a construction method and device of a bipolar disorder experimental animal model and application, the construction method comprises the following steps: selecting a healthy experimental animal to carry out environmental adaptation feeding before modeling, then carrying out sleep deprivation stimulation for 3-5 days continuously, and carrying out sleep deprivation stimulation for 15-18 hours continuously and 6-9 hours for rest every day so as to freely eat and feed water; and after the sleep deprivation stimulation is finished, evaluating the surface validity of the disease model for the experimental animal by adopting behavioral test. The construction method provided by the invention is simple to operate and easy to repeat, can better simulate the disease of a clinical bipolar disorder patient, and provides a new model normal form for pathogenesis research and clinical drug screening of the bipolar disorder, and the disease model can be maintained for a long time.

The invention belongs to the technical field of medical experimental animal models, and particularly relates to a construction method of a rabbit ear acne model for studying acne pathogenesis and drug curative effect. A healthy New Zealand large-ear white rabbit is selected, a testosterone solution is subcutaneously injected to induce endocrine disorder, oleic acid is smeared at an opening of an external auditory canal on the inner side of an ear, dermatobacterium acnes suspension is subcutaneously injected, and whether acne-like lesions such as erythema, papule and comedo appear on the skin of the ear or not is observed. The method is easy and convenient to operate, low in cost, good in repeatability, capable of simulating the pathological process of human acne and suitable for acne pathogenesis research and drug screening.

The invention belongs to the technical field of medical experimental animal models, and discloses a small animal model for skull base high-flow cerebrospinal fluid leakage and skull base reconstruction as well as a construction method and application of the small animal model. The technical obstacle that due to the fact that the nasal cavity of a small animal is narrow and the turbinate structure is complex, surgical instruments cannot reach the skull base through the nose is overcome, meanwhile, a modeling and repairing area is arranged on the rear nasal meatus and the top wall of the nasopharynx, and the temperature and humidity conditions and environment of the nasal mucosa are reserved; and the microenvironment for tissue healing after the endoscopic transnasal skull base surgery is restored on the pathophysiological level. The dissected marking points are clear, and compared with narrow anterior skull base low-flow cerebrospinal fluid leakage of small animals, the standardized bone defect constructed in the middle skull base butterfly saddle area can cause continuous and high-flow cerebrospinal fluid leakage; autologous bone flap and free mucous membrane repair is used, the method is the same as current clinical practice, and a new platform can be provided for screening of skull base repair materials or operation evaluation and retrograde intracranial infection research after an operation.

The invention belongs to the technical field of experimental animal models, and particularly relates to a construction and analysis method of a zebra fish heart failure model. The invention discloses a construction method of a zebra fish heart failure model. The construction method comprises the following steps: S1, pretreating a zebra fish embryo; and S2, putting the zebra fish embryos pretreated in the step S1 into an exposure solution for exposure, thereby completing the construction of the zebra fish heart failure model. According to the construction and analysis method of the zebra fish heart failure model, accurate induction and dynamic monitoring of heart failure phenotypes are achieved through a standardized drug treatment process and a multi-mode heart function evaluation system, and an efficient platform is provided for cardiovascular drug screening and toxicity evaluation. The construction and analysis method of the zebra fish heart failure model further extends to the field of medicine and functional food heart protection efficacy evaluation, and objective grading authentication of food and medicine efficacy is achieved.

The invention relates to the technical field of medical experiment animal models, in particular to an animal experiment model and method for calcium signal recording, and the model comprises the following steps: introducing a fluorescent marker from a specific area of a selected target body into neurons of the target body, and arranging a microscopic camera fixing seat at the specific area of the target body, and observing the brain activity of the target body by using a microscope camera. According to the invention, intravenous administration and calcium signal recording model animal construction is realized, and subsequent research on drug effects and treatment mechanisms is facilitated by observing the change of calcium signals at the moment of drug intravenous blood vessel infusion.

The invention belongs to the technical field of medical experimental animal models, provides a construction method of a dry age-related macular degeneration animal model, and aims to break through the technical bottlenecks of long construction period, high cost and incomplete pathological feature coverage of an existing model. D-galactose is used for inducing glycosylation end product accumulation and mitochondrial dysfunction, oxidative stress, RPE metabolic disorder and inflammation microenvironment in the dry AMD pathogenesis process can be synchronously simulated, core pathological characteristics such as retina glass membrane wart deposition, RPE atrophy, retina and visual function damage and the like can be accurately reproduced, meanwhile, a multi-dimensional verification system is matched, and the method has the advantages that the method is simple and convenient to operate and high in practicability. The method is suitable for preclinical evaluation of personalized treatment strategies; besides, the method is short in modeling period, the animal model meeting the requirement can be obtained within 8 weeks, the cost advantage is outstanding, and an efficient and reliable experimental animal model can be provided for dry AMD treatment research.

This invention discloses a method for establishing a mouse model of outer retinal tubular structures, which is obtained by specifically knocking out the Lss gene in the mouse retina. This invention utilizes CRISPR / Cas9 gene editing technology to construct a mouse model of outer retinal tubular structures by specifically knocking out the Lss gene in the retina. The mouse model of outer retinal tubular structures constructed by this method is similar to the clinical phenotype of this type of retinal disease, providing a relatively ideal experimental animal model for studying the developmental regulation of the mammalian retina and the pathogenesis of retinal degeneration.

The invention relates to the technical field of experimental animal models, in particular to an establishment method and application of a rat radioactive cataract model. According to the invention, a rat cataract model induced by irradiation of X-rays with different doses (10 Gy, 20 Gy and 30 Gy) is constructed. Through multi-dimensional evaluation such as general situation observation, slit lamp inspection and histopathologic analysis, the influence of ionization radiation (IR) on the crystalline lens is systematically observed. The animal model successfully reproduces pathological manifestations of different radiation-damaged crystalline lenses, and an experimental basis is provided for further research on pathogenesis of radiation-induced cataract.

The invention discloses an application of a NanoLuc luciferase double-subunit complementary system in construction of an experimental animal model. The genome of the experimental animal model contains a NanoLuc enzyme large subunit LgBiT encoding gene and stably expresses LgBiT; correspondingly, a tested object used for invading the experimental animal model or connected into the experimental animal model is in fusion connection with NanoLuc luciferase small subunit HiBiT polypeptide serving as a label or a NanoLuc luciferase small subunit HiBiT coding gene serving as a reporter gene, and LgBiT and HiBiT are specifically combined in the experimental animal model and recombined to form the NanoLuc enzyme with catalytic activity. A strong bioluminescence signal is generated under the action of a furazine substrate, so that high-sensitivity, non-invasive and real-time dynamic imaging of in-vivo distribution, loading capacity and diffusion path of a detected object is realized. The invention also discloses a gene editing system for constructing the LgBiT transgenic mouse.

The present invention relates to the technical field of experimental animal models, and discloses an animal model of lung and spleen qi deficiency syndrome based on the theory of "mother disease and child", and the model realization method includes the following steps: S1, material selection and grouping; S2, model replication; S3, model evaluation; S4, index detection; S5, statistical processing; S6, model verification. The present invention gives model rats a high-fat and low-protein feed, and puts them in a homemade swimming pool to swim to exhaustion after daily weight bearing, and evaluates the model after 6 weeks; the modeling method does not directly damage the lungs of rats, and the spleen qi deficiency process caused by it is very mild, and the onset characteristics of the complex deficiency syndrome course are prolonged, and at the same time, spleen qi deficiency comes first, and lung qi deficiency comes later, which is in line with the basic mechanism of the formation of lung and spleen qi deficiency syndrome in traditional Chinese medicine; the method establishes an animal model of lung and spleen qi deficiency syndrome, and the etiology and pathogenesis are accurate, and it is non-invasive, stable, and easy to evaluate, which broadens the application scope of the original modeling method and lays a foundation for the mechanism research of the method of accompanying soil to produce gold.

The invention relates to the technical field of experimental animal model construction in biomedical research, and discloses a common bile duct flow limiting tube for constructing a chronic cholestasis rat model and a construction method, the flow limiting tube comprises a hard tubular body and a soft protective fixing wing wrapping the tubular body, the inner diameter of the tubular body is 0.12-0.15 mm, and the outer diameter of the tubular body is 0.12-0.15 mm. The length of the tubular body is 0.5 to 0.8 cm; protruding fixing rings are arranged at the two ends of the protection fixing wing, and the total outer diameter of the flow limiting pipe is smaller than or equal to 0.7 mm. The common bile duct flow limiting tube is implanted into the specified position of the common bile duct of an experimental animal through a precise operation, precise control over bile flow is achieved, and therefore a standardized animal model capable of highly simulating the human chronic cholestatic liver disease in the aspects of the pathological process, physiological compensation and systematic expression is established. The model and the construction method thereof can be directly applied to multiple directions of liver pathophysiology mechanism research, drug target verification, new drug curative effect and safety evaluation and the like.

This application relates to a method for constructing and applying an acute anxiety model for experimental animals. By injecting exogenous parathyroid hormone-related proteins into the experimental animals, the animals develop anxiety symptoms within a short period of time, thereby obtaining an acute experimental animal model with anxiety symptoms. The acute anxiety model for experimental animals obtained in this application has the advantages of rapid effectiveness, short modeling time, and a distinct anxiety phenotype. This method overcomes the problems of traditional animal acute anxiety models, such as the tendency to incur additional injuries during the modeling process, poor ventilation of experimental animals, differences in restraint pressure, and additional dizziness in experimental animals. This method facilitates the study of the mechanisms of anxiety disorders and drug development.

The invention relates to the technical field of medical experimental animal models, in particular to a construction method of an animal model for researching jaw cyst, which comprises the steps of experimental animal selection, surgical site preparation, bone windowing operation, cyst induction material implantation, wound suture, postoperative care and observation, and simulation of in-vivo development of jaw cyst by an implant. The invention provides a jaw cyst animal model which is high in modeling success rate, good in stability, highly similar to pathological characteristics of a bone cavity of a human jaw cyst and simple and convenient to operate, and a construction method of the jaw cyst animal model. A reliable experimental model is provided for pathogenesis research, pathological process discussion, drug research and development, treatment method evaluation and the like of the jaw cyst.

The invention relates to a tx-j mouse animal model construction method based on phlegm-blood stasis syndrome cognitive impairment, and belongs to the technical field of medicine. The tx-j mouse is firstly fed with high-fat diet to make a hyperlipidemia state, then an ice-water bath method is adopted to make a'blood stasis' model, and finally the tx-j mouse animal model for the cognitive impairment of the syndrome of intermingled phlegm and blood stasis is constructed. After the model is successfully constructed, firstly observing the state and tongue color of the mouse, carrying out a water maze experiment, then detecting blood rheology indexes, blood fat indexes, tissue and serum copper contents and inflammatory factors, and observing brain pathological changes of the mouse. The high-fat feed is used for feeding to make a hyperlipidemia state, which is equivalent to'turbid phlegm 'of traditional Chinese medicine. The'blood stasis' model is manufactured by adopting an ice-water bath method on the basis of the traditional Chinese medicine theory of'cold coagulation and blood stasis', the modeling mode makes up the defects of the WD cognitive impairment model without combination of diseases and syndromes at present, and an effective experimental animal model is provided for revealing the pathogenesis of hepatolenticular degeneration cognitive impairment and evaluating the curative effect of traditional Chinese medicine.

The invention discloses a micro-plastic exposure health risk detection method with desulfovibrio as a biomarker. The method comprises the steps of fecal sample collection, DNA extraction, desulfurization vibrio abundance detection and risk judgment. Based on the experimental conclusion that microplastic exposure can significantly enrich intestinal desulfurization vibrio, and the abundance of the bacterium is positively correlated with neuropathy and cancer related metabolites, 16S rRNA sequencing is adopted to detect the abundance of the desulfurization vibrio, and health risk assessment is achieved through comparison with a control group. The method has the advantages of noninvasive property, specificity and convenience, can be used for human microplastic exposure screening or experimental animal model research, and provides an effective tool for microplastic health risk early warning.

The application relates to an induced type 2 diabetes mellitus feed and application thereof in establishing a type 2 diabetes mellitus animal model, and relates to the field of experimental animal models, and particularly relates to an induced type 2 diabetes mellitus feed and application thereof in establishing a type 2 diabetes mellitus animal model. The application aims at solving the problems of long modeling time, instability and easy change into a type 1 diabetes mellitus model of the existing type 2 diabetes mellitus animal model establishing method. The feed comprises desulfurization vibrio powder, symbiotic clostridium powder and high-fat high-sugar feed. The method comprises the following steps: drying desulfurization vibrio liquid and symbiotic clostridium liquid into powder, uniformly mixing the powder and the high-fat high-sugar feed, and extruding into a column shape by using an extrusion molding machine. The application significantly shortens the establishment time of the type 2 diabetes mellitus animal model, does not need to inject a high-dose STZ, and does not cause the type 1 diabetes mellitus model of absolute insulin deficiency of rats in the case of using a higher concentration of STZ induction. The induced type 2 diabetes mellitus feed is used for establishing the type 2 diabetes mellitus animal model.

The application provides a construction method of a zebrafish model of diabetic cerebral hemorrhage sequelae for high-throughput drug screening, and belongs to the technical field of biotechnology.The first zebrafish model capable of comprehensively simulating the complex pathological phenotypes of clinical diabetic cerebral hemorrhage sequelae is successfully constructed, and the blank of the research model in the field is filled.The pathological changes of the model are highly consistent with the symptoms of the patients with clinical diabetic cerebral hemorrhage sequelae, such as glucose metabolism disorder, pancreatic beta cell damage, cerebral vascular injury and hemorrhage, brain cell apoptosis, inflammatory reaction and behavior abnormality, and the limitation that the existing single disease model cannot simulate the synergistic pathogenesis of diabetes and cerebral hemorrhage is overcome, so that a reliable experimental animal model is provided for high-throughput screening of active ingredients against the disease.

The invention provides a vertebral artery type cervical spondylosis animal model building method, and belongs to the technical field of medical experiment animal models, and the method comprises the following steps: S1, experiment animal pretreatment: carrying out anesthesia treatment on an experiment rat, and then preparing skin on the neck; s2, molding the experimental animal by injecting a molding agent, namely injecting the molding agent by taking the cervical vertebra C2 transverse process level of the rat as a needle insertion point; and S3, performing model evaluation. According to the method, a traditional hardening agent molding method is optimized and improved, the problems existing in the prior art are solved, and a more reliable experimental basis is provided for CSA research in the aspects of accuracy, safety, stability, reliability and clinics.

This invention belongs to the field of biomedical experimental animal model construction technology, specifically relating to a method for constructing a rat model of radiation-induced recurrent dermatitis (RRD). This invention successfully induces recurrent skin inflammation localized to the original irradiated area in rats that have undergone initial radiation injury by inducing drug therapy at a specific induction starting point, thus obtaining a rat model of RRD. The model constructed by this method successfully reproduces the recurrent characteristics of RRD, with inflammation only occurring in the previously irradiated area, while the unirradiated skin remains intact, exhibiting good clinical fit and stability. This model provides a reliable in vivo experimental platform for in-depth research into the pathogenesis of RRD, screening intervention targets, and evaluating treatment regimens.

The invention belongs to the technical field of medical experimental animal models, and particularly relates to a stable and high-reproducibility severe acute pancreatitis mouse model construction method, a quantitative evaluation system and application thereof, and the method comprises the following steps: selecting a male C57BL / 6 mouse of 6-8 weeks old, adaptively feeding for one week, and then carrying out model induction; the preparation method comprises the following steps: carrying out intraperitoneal injection on leptofrog at the dosage of 100 mu g / kg once every 1 hour, and continuously injecting for 7 times; within 2 hours after completion of the seventh time of rain frog element injection, lipopolysaccharide is injected into the abdominal cavity, and the dosage is 12 mg / kg; pathological and physiological index evaluation is carried out on the mouse 24 hours after the first time of rain frog element injection, and multi-batch verification experiments prove that the inter-batch fluctuation range of the model constructed by the invention on the death rate, the pathological score, the weight change and other key indexes is controlled within + / -5%, so that the repeatability and comparability of experimental results are ensured.

The invention belongs to the field of experimental animal models, and particularly relates to a feed for inducing type II diabetes mellitus and application thereof, the feed comprises the following components by weight: 450-550 parts of conventional components, 10-150 parts of rapeseed oil with trans fatty acid content of 63-67 g / L, 30-170 parts of lard, and 170-180 parts of sucrose; the conventional components consist of the following components in parts by weight: 200 parts of casein, 3 parts of L-cystine, 72.8 parts of corn starch, 100 parts of maltodextrin, 50 parts of cellulose, 25 parts of soybean oil, 10 parts of trace elements, 10 parts of vitamins, 2 parts of choline bitartrate, 0.05 part of a coloring agent, 13 parts of calcium hydrophosphate, 5.5 parts of calcium carbonate and 16.5 parts of potassium citrate. Compared with a commercially available feed D12451, the feed provided by the invention can efficiently induce a stable and typical type II diabetes rat model.

The invention belongs to the technical field of medical experimental animal models, and particularly relates to a construction method of a spleen and stomach damp-heat syndrome chronic atrophic gastritis animal model. The construction method comprises the following steps: firstly, performing spleen and stomach damp-heat modeling on a tested animal to obtain spleen and stomach damp-heat syndromes, and then performing chronic atrophic gastritis induction. According to the specific three-step atrophic gastritis induction method, the clinical pathological process of inflammation caused by stimulation, gastric mucosa atrophy caused by damp heat and blood stasis for a long time and intestinal metaplasia can be accurately copied, the clinical pathological process is highly matched with the stage progress characteristic of clinical chronic atrophic gastritis, and the model is high in success rate, good in stability and high in repeatability.

The invention relates to the technical field of experimental animal model construction, and particularly discloses an ulcerative dermatitis mouse model construction method which comprises the following steps: firstly, feeding a mouse with a high-fat feed A for 4 weeks; in the fifth week, the mixed feed of the high-fat feed A and the high-fat feed B lacking the vitamin B7 is replaced for feeding; from the sixth week to the twelfth week, high-fat feed B lacking vitamin B7 is used for feeding; in the sixth week to the tenth week, the mice are placed in a smoking device to be smoked for 2-3 h every day; in the tenth week to the twelfth week, vancomycin with the concentration of 100-120 mg / ml is injected into the tail vein of the mouse, the injection frequency is 2-3 times per week, and the injection amount is 40-60 mg / kg. The construction method of the ulcerative dermatitis mouse model provided by the invention can accurately simulate the pathogenesis of human ulcerative dermatitis, and provides a reliable experimental basis for researching the pathogenesis and treatment means of the ulcerative dermatitis.

The invention relates to the technical field of biological medicine, and discloses a polyorthoester in-vivo analysis method and application thereof, and the method comprises the following steps: S1, determining and selecting an experimental animal model; s2, performing injection administration, selecting experimental animal models at different time points after administration for sampling, and tracking the degradation process of the polyorthoester through the sampling; s3, extracting and separating polyorthoester and a degradation product thereof, and performing qualitative and quantitative analysis on the degradation product; and S4, establishing a standard curve and a mass concentration relationship according to an analysis result. The invention further discloses application of the analysis method in preparation of ophthalmic disease drugs, pain relieving drugs, polypeptide and protein drugs and vaccines. By performing histological analysis on experimental animals, the influence of in-vivo degradation of the polyorthoester on tissues can be evaluated, so that the safety of the medicine is improved. By detecting biological indexes in the experimental animal model, the influence of degradation in the polyorthoester on the biological process can be evaluated, so that the effectiveness of the medicine is improved.

The invention discloses a mouse model for detecting an endogenous pain regulation function as well as a construction method and application of the mouse model, and relates to the technical field of experimental animal models. The construction method of the mouse model comprises the following steps: screening out mice with normal mechanical pain thresholds for model construction by measuring the mechanical pain thresholds of the mice; injecting a complete Freund's adjuvant into the front limbs of the screened mice or clamping the front limbs by using a clip; capsaicin is injected into the hind limbs of the mouse, and the mouse model for detecting the endogenous pain regulation function is obtained through pain behavior verification. The construction method of the mouse model is simple, the success rate of model construction is high, and the mouse model has important value and significance for pathological research of chronic pain and screening and evaluation of drugs.

The invention discloses a drug screening method based on a comprehensive survival index and application thereof, and belongs to the technical field of drug screening, and the drug screening method comprises the following steps: (1) constructing a disease experimental animal model, and obtaining the survival time, the survival rate, the tumor quality, the net body quality and the pulmonary nodule number of an experimental animal after the experimental animal is administered with a drug; (2) acquiring area data on a net body mass change rate curve according to the net body mass data; acquiring tumor control coefficient data according to the tumor quality and the net body quality; and (3) standardizing the data of the survival rate, the survival time, the area on the net body mass change rate curve and the number of pulmonary nodules by using a summation normalization method. The method provided by the invention can accurately judge the treatment effect of each medicine on diseases and the protection condition of each medicine on body health, objectively reflect the progress condition and prognosis effect of the diseases, screen out the medicine with a good comprehensive treatment effect, and provide more accurate data support for clinical and experimental research.

The present application belongs to the field of biomedical technology, and relates to a construction method of an experimental animal model and a constructed experimental model, in particular to a method for constructing a kidney humanized mouse model based on human cells and a constructed kidney humanized mouse model. The construction method comprises the following steps: injecting mesenchymal stem cells, human umbilical vein endothelial cells and human renal tubular epithelial cells separated from urine into immunodeficient mice subcutaneously or subcapsularly to obtain a humanized kidney vascular unit mouse model communicating with the host. The model construction has the following characteristics: the cells used are derived from urine, have the characteristics of sufficient clinical source and convenient sampling, and the kidney source cells derived from urine can represent a unique individual alone, can be used to establish an individualized kidney humanized mouse model based on patients, and have the potential to be applied to individualized precision medical research; the model can form a functional human kidney vascular unit in mice, and has great application prospects in individualized precision medical treatment of kidney disease and human kidney specific virus infection research.

The application discloses an experimental animal modeling auxiliary device, which comprises a feeding cage, a feeding box is slidably installed on the inner side of the feeding cage, a partition plate is fixedly installed in the feeding box, the partition plate divides the feeding box into a feed cavity and a water cavity, a height adjusting mechanism is arranged below the feeding box, and the height adjusting mechanism is used for adjusting the height of the feeding box; a plurality of threaded grooves are formed in the outer wall of the feeding box, a restraint part is detachably installed in the threaded grooves, and the restraint part is used for fixing the forelimbs of the feeding animal; a pressurizing mechanism is arranged on the top of the feeding cage and is correspondingly arranged with the restraint part, and the pressurizing mechanism is used for increasing the weight of the feeding animal. The application simulates the state of the human knee joint from two aspects of mechanical characteristics and motion characteristics, thereby being closer to the pathogenesis characteristics of human knee osteoarthritis, better researching the pathogenesis and process of knee osteoarthritis, and better assisting the modeling of knee osteoarthritis of rats, so that the modeling is more scientific and reasonable.