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67 results about "Semen sample" patented technology

A system and method for automated detection of semen quality

This invention relates to the field of beauty and skincare, and discloses an automated system and method for detecting semen quality, comprising: a morphological defect rate calculation module for calculating the morphological defect rate corresponding to a target semen sample; a dysfunctional sperm identification module for identifying dysfunctional sperm in the target semen sample; a reproductive function scoring module for evaluating the reproductive function score corresponding to the target semen sample; a dynamic motility potential scoring module for configuring a suitable culture medium for the target semen sample, culturing the target semen sample in the suitable culture medium, recording the sperm viability baseline parameters during the culture process, calculating the sperm survival rate of the target semen sample, and evaluating the dynamic motility potential score corresponding to the target semen sample; and a semen quality analysis module for generating a semen quality analysis report corresponding to the target semen sample. This invention can improve the accuracy of semen quality detection.
Owner:THE THIRD AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIVERSITY (GUANGZHOU SEVERE MATERNAL TREATMENT CENTER GUANGZHOU ROUJI HOSPITAL)

Methods of identifying, differentiating between, and / or sorting cells

PendingUS20260193604A1Semen samplePhysiology
The present disclosure relates to methods of identifying, differentiating between and / or sorting sperm cells, or more particularly, X-chromosome bearing sperm (X-CBS) and Y-chromosome bearing sperm (Y-CBS) cells, in a sperm sample, the methods comprising determining a level of a Reactive Oxidant Species and / or a Cellular Change mediated thereby (ROSCC) in each of a plurality of sperm cells in the sperm sample; and based on the determined ROSCC levels, identifying, differentiating between and / or sorting X-CBS and Y-CBS cells in at least a portion of the plurality of sperm cells. Also described are enriched or purified X-CBS and Y-CBS cells, and uses thereof.
Owner:UNIVERSITY OF TASMANIA

A method and system for evaluating local cattle semen quality based on multi-source data analysis

The present application belongs to the technical field of bull semen quality evaluation, and particularly relates to a local bull semen quality evaluation method and system based on multi-source data analysis. The method comprises: when real-time data corresponding to a current semen sample is acquired, executing a quality evaluation process to generate a comprehensive score of the current semen sample; based on the offset amplitude of sample data generated by the evaluation model in the benchmark test, determining a main parameter and at least one subsidiary parameter from a plurality of to-be-tested parameters associated with the current semen sample. The present application calculates a subsidiary score according to the subsidiary parameter, and adjusts the subsidiary score by using an external parameter to generate a comprehensive score; and a multi-dimensional dynamic evaluation framework is constructed to consider a plurality of to-be-tested parameters of the semen itself, and the external parameter is quantified and integrated into the final score, so that the evaluation result can dynamically adapt to different environments and individual conditions, and overcome the limitation of single evaluation dimension in the prior art.
Owner:广西壮族自治区畜禽品种改良站

Sperm quality analyser

ActiveCN309757395SBiotechnologySemen sample
1. Name of the product in this design: Sperm Quality Analyzer. 2. Purpose of this design: The product is intended for use by research institutions and medical institutions for sperm concentration detection, motility analysis, sperm morphology identification, and determination of semen pH and DNA fragmentation rate in semen samples. 3. The key design feature of this product is its shape. 4. The image or photograph that best illustrates the design's key points: 3D rendering 2.
Owner:BEIJING SPERMCAPTURER BIOTECHNOLOGY CO LTD

Centrifuge-free sperm preparation in an intelligent automated in vitro fertilization and intracytoplasmic sperm injection platform

A method of artificial-intelligence-based robotic pipetting for spermatozoa preparation includes positioning a vessel containing a semen sample within a staging mechanism. The method includes using a robotic pipettor to make at least two droplets within a dish on the staging mechanism. The method includes using the robotic pipettor to connect the at least two droplets with a medium channel according to a programmable design commanded by an artificial intelligence / machine learning system (AI / ML system). The method includes using the robotic pipettor to deposit a quantity of sperm from the semen sample into one of the droplets. The method includes using the AI / ML system to optically scan the quantity of sperm to produce first and second image objects using an imaging system that includes a microscopy system, a camera system, and a lighting system. Creation of the image objects is separated by a specified time duration.
Owner:CONCEIVABLE LIFE SCI INC

Sperm taking cup and sperm taking cup assembly

The semen collection cup comprises a cup body and a cover body, the cover body comprises a cup cover and a silica gel layer, the bottom wall of the cup cover is covered with the silica gel layer, the silica gel layer can be embedded into the cup body and abut against the inner wall of the cup body, and the outer wall of the cup body is covered with a heat preservation coating. The structure can improve the sealing performance and prevent the seminal fluid sample from leaking in the transportation process; the cup body can be conveniently closed and opened, one-hand operation is facilitated, the heat preservation effect can be improved, and the influence of temperature change on the activity and quality of a sample is reduced.
Owner:THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE

Improved semen DNA collection card for assisted reproductive technology

ActiveCN224441368USemen sampleAnimal science
This utility model discloses an improved semen DNA collection card for assisted reproductive technology, belonging to the field of medical supplies technology. It includes a folding card with an upper cover, a lower cover, and a bottom surface. The bottom surface is located between the upper and lower covers. The lower cover has a sampling filter paper surface, and a PVC diaphragm is provided in the middle of the sampling filter paper surface to divide it into a pre-processing semen collection area and a post-processing semen collection area. This utility model stores the patient's unprocessed semen in the pre-processing semen collection area and the processed semen in the post-processing semen collection area. The PVC diaphragm between the two areas prevents interference and cross-contamination between the two semen samples, facilitating DNA comparison before and after semen processing. The folding card also facilitates transportation and transfer, allowing for the storage of both pre- and post-processing semen within a single card, which is beneficial for clinical research.
Owner:GUANGDONG WOMEN & CHILDREN HOSPITAL

Information processing method, device and equipment for detecting sperm quality and medium

The application discloses an information processing method and device for detecting sperm quality, equipment and medium, applied to a computer device, relates to the field of biomedical detection, and comprises the following steps: injecting an original semen sample into a preset microfluidic chip to dilute the original semen sample, and collecting multi-modal diluted sample data; performing parallel feature analysis on the multi-modal diluted sample data to determine corresponding multiple sperm characteristics; performing feature fusion on the multiple sperm characteristics based on a preset feature weight distribution network to obtain sperm fusion characteristics; determining corresponding several sperm quality parameters based on the sperm fusion characteristics, and determining the sperm quality of the original semen sample based on the several sperm quality parameters. Therefore, the detection efficiency and result reliability can be improved through highly automated synchronous multi-modal data acquisition and deep fusion analysis.
Owner:RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE

Sample analyzer

The invention is applicable to the field of in-vitro diagnostic equipment, and discloses a sample analyzer. The sample analyzer comprises a sample introduction device, a sample distribution device, a first visible component detection device, a second visible component detection device and a controller, wherein the first visible component detection device comprises a first microscopic imaging device. The controller is configured to at least output a kinetic analysis result of sperms in the semen sample according to an image obtained by executing a first shooting action on the semen sample by the first microscopic imaging device; and at least outputting a morphological analysis result of at least part of the visible components in the first body fluid sample according to detection data obtained by performing the visible component detection action on the first body fluid sample by the second visible component detection device. According to the invention, one sample analyzer can be used for carrying out visible component analysis on a semen sample and another type of body fluid sample, so that the purchase, use and maintenance cost of the sample analyzer for analyzing the semen sample can be reduced.
Owner:SHENZHEN MINDRAY BIO MEDICAL ELECTRONICS CO LTD

Method for evaluating damage of ionizing radiation to quality of male sperms

The invention discloses a method for evaluating damage of ionizing radiation to male sperm quality, which belongs to the technical field of reproductive biology, and comprises the following steps: establishing a dose-effect database model between ionizing radiation dose and male sperm quality based on a logistic regression model, determining a mapping relation between sperm quality rating and fertility recovery average time; collecting a to-be-detected semen sample exposed by ionizing radiation, comparing the to-be-detected semen sample with the dose-effect database model, evaluating the male sperm quality rating, and predicting the fertility recovery time based on the male sperm quality rating and the mapping relation.
Owner:WOMEN S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE

A sperm-specific mRNA-cSNP primer composition, kit and method based on SNaPshot technology

This invention discloses a semen-specific mRNA-cSNP primer composition, kit, and method based on SNaPshot technology, belonging to the field of molecular identification technology. The primer composition provided by this invention includes amplification primers with nucleotide sequences as shown in SEQ ID NO. 1-34 and single-base extension primers as shown in SEQ ID NO. 35-52. This invention further provides a method for identifying human semen samples, including extracting sample mRNA, reverse transcription to obtain cDNA, performing an amplification reaction using amplification primers, and then performing a single-base extension reaction using single-base extension primers. Experimental results show that the identification method of this invention has advantages such as high specificity, high sensitivity, and good reproducibility, and can accurately identify individual semen donors, which is of great significance for achieving accurate semen-related criminal investigations and forensic identification.
Owner:ACADEMY OF FORENSIC SCIENCE +1

Method and system for predicting fertilized egg or embryo abnormalities through sperm movement analysis

The present invention relates to a method and system for predicting fertilized egg or embryo abnormalities through sperm movement analysis. Through the present invention, idiopathic male infertility or abnormalities in sperm-derived fertilized eggs or embryos can be effectively predicted by obtaining sperm movement information from a semen sample of a subject through artificial intelligence model-based analysis and then utilizing the information as abnormality prediction information.
Owner:COLLEGE OF MEDICINE POCHON CHA UNIV IND ACADEMIC COOP FOUND +1

Semen sample quality management system based on federated learning and dynamic time sequence prediction

The invention discloses a semen sample quality management system based on federated learning and dynamic time sequence prediction, which is characterized in that a data acquisition module (100) is used for cleaning received original semen sample detection data, a federated learning cooperation module (200) adopts an improved Paillier homomorphic encryption algorithm to carry out encryption transmission on local model gradient parameters, and a dynamic time sequence prediction module (200) is used for carrying out dynamic time sequence prediction on the local model gradient parameters; the dynamic time sequence prediction module (300) is used for extracting quality characteristics with a time sequence dependency relationship from detection data of a semen sample and carrying out online incremental training on a prediction model; the multi-modal data fusion module (400) is used for extracting a genome feature sequence of a semen sample and analyzing environmental parameters stored in the sample; and the quality evaluation decision module (500) fuses the time sequence prediction model and the genome feature sequence. According to the method, multi-center data collaborative modeling is achieved through a federated learning architecture, the online incremental learning ability is achieved in combination with the multi-modal data fusion technology, the prediction model can be continuously optimized, and the method effectively adapts to the change of sample features.
Owner:CHONGQING INST OF POPULATION & FAMILY PLANNING SCI & TECH

An automated sperm density detection pool integrating sample mixing and temperature control functions

This invention relates to the field of sperm detection technology, specifically disclosing an automated sperm density detection chamber integrating sample mixing and temperature control functions. The chamber comprises, from bottom to top, a light-transmitting bottom layer, a microchannel layer, and a light-transmitting cover layer. The light-transmitting bottom layer has, from bottom to top, a glass substrate layer, an ITO heating electrode layer, a first light-transmitting insulating layer, a first ITO mixing electrode layer, and a second light-transmitting insulating layer. The light-transmitting cover layer has, from top to bottom, an upper glass surface layer, a second ITO mixing electrode layer, and a third light-transmitting insulating layer. The microchannel layer forms microchannels, and the light-transmitting cover layer has an inlet port and an exhaust port communicating with the microchannels. This invention achieves stable constant temperature control of the semen sample within the microchannels, effectively avoiding the adverse effects of environmental temperature fluctuations on sperm characteristics and detection results. Furthermore, it enables in-situ automatic mixing of the semen sample, improving the accuracy and repeatability of sperm density detection results.
Owner:QINGDAO WOMEN & CHILDREN HOSPITAL

Sperm quality detection device and preparation method thereof

The invention discloses a sperm quality detection device and a preparation method thereof. The sperm quality detection device comprises a base material, a sperm activity detection module, an SP10 detection module and a PSA detection module, the sperm activity detection module comprises a containing cavity and a convex lens, the containing cavity is provided with a detection plane, the convex lens is configured to slide to a sample adding hole along with a sliding assembly and amplify an image of the detection plane, and the SP10 detection module comprises a P10 colloidal gold test strip. And the PSA detection module comprises a PSA colloidal gold test strip. The invention provides a special counting integrated detection device for sperm acrosomal enzyme SP10 protein and prostate specific antigen PSA of a sperm sample. The method is simple to operate, can provide a detection result in a short time, can completely detect and judge the result by a detected person, and is suitable for primary medical units and on-site rapid detection.
Owner:GUANGZHOU LANGKUN BIOTECHNOLOGY CO LTD

Screening system and method for cryptic sperm based on magnetic bead capture and fluorescent recognition

PendingCN122754288ASemen sampleMagnetic bead
The application provides a hidden sperm screening system and method based on magnetic bead capture and fluorescent identification, and is applied to the technical field of magnetic bead fluorescence analysis. A sperm sample is incubated with high-magnetic-saturation first immunomagnetic beads and low-magnetic-saturation second immunomagnetic beads in an incubation module, and the two kinds of magnetic beads are coupled with anti-sperm antibodies and anti-non-sperm cell antibodies respectively. A magnetic field generating module applies an alternating magnetic field to a separation area and synchronously injects sheath liquid, and uses the difference in magnetic response characteristics to retain the complex combined with sperm and to flush away the complex combined with non-sperm cells. A dye introduction module introduces membrane impermeable and permeable dyes under the constraint of a magnetic field, and obtains fluorescent characteristics of membrane-intact and membrane-damaged sperm which can be distinguished. An imaging module performs multi-channel fluorescence imaging, an image analysis module extracts positive events conforming to morphology and fluorescent logic, and finally outputs sperm count parameters and membrane integrity classification parameters synchronously.
Owner:HUZHOU LIYUAN MEDICAL LAB CO LTD

Application of pseudomonas as marker in evaluation of bull semen quality

The invention discloses application of pseudomonas as a marker in evaluation of bull semen quality, and belongs to the technical field of animal breeding and microbiomics. The relative abundance of Pseudomonas in a bull rumen fluid with high semen quality is significantly higher than the relative abundance in a bull rumen fluid with low semen quality. By detecting the relative abundance, the bull semen quality can be evaluated, and the reproductive performance can be reliably judged on the premise of not depending on a semen sample. Evaluation can be carried out before semen collection for the first time or in a breeding candidate period, potential low-fecundity individuals are screened out in advance, and the breeding risk is reduced.
Owner:INST OF ANIMAL SCI & VETERINARY MEDICINE SHANDONG ACADEMY OF AGRI SCI +1

Systems and methods for rapid nucleic acid extraction, purification and analysis from semen

Disclosed are processes and kits for rapid nucleic acid extraction from a nucleic acid-containing material, such as a bone, tooth or semen sample. For bone and tooth process involves providing the nucleic acid-containing material in a form suitable for nucleic acid extraction, adding a lysis buffer to the nucleic acid-containing material to obtain a mixture, mixing the mixture in a manner equivalent for about 30 seconds or longer and separating the mixture by centrifugation to obtain a liquid supernatant. The liquid supernatant contains the extracted nucleic acids which can be used for analysis including STR profiling by conventional or rapid DNA analysis. For semen the processes and kits involve applying an appropriate amount of sperm disruptive agent.
Owner:ANDE CORP

Sample analyzer

The present application is applicable to the field of in-vitro diagnostic devices. Disclosed is a sample analyzer. The sample analyzer comprises: a feeding device, a sample distribution device, a microscopic imaging device and a controller, wherein the controller is configured to: on the basis of an image obtained by means of the microscopic imaging device executing a first photographing action on a semen sample, output at least a motility analysis result of sperm in the semen sample; and on the basis of an image obtained by means of the microscopic imaging device executing a second photographing action on a first body fluid sample, output at least a morphological analysis result of at least some formed elements in the first body fluid sample. A first sample container and a second sample container are two mutually independent sample containers, and a first carrier and a second carrier are two mutually independent carriers or the same carrier. The sample analyzer of the present application can perform formed-element analysis on a semen sample and another body fluid sample, thereby facilitating a reduction in purchase, usage and maintenance costs of sample analyzers that can be used for semen sample analysis.
Owner:SHENZHEN MINDRAY BIO MEDICAL ELECTRONICS CO LTD

Stable medium and method for prolonging survival time of human semen sample

The invention discloses a stable medium for prolonging the survival time of a human semen sample and a method thereof. The medium is composed of a pH buffer agent, an inorganic salt, an organic compound and amino acid with oxidation resistance. When the human semen is mixed with the stable medium, the survival time of the semen can be effectively prolonged to 72 hours at most when the temperature is kept within the range of + / -20% of the human body temperature.
Owner:阿什温·拉马钱德兰

Constant-temperature semen storage box

The invention belongs to the technical field of livestock breeding equipment, and discloses a constant-temperature semen storage box which comprises a box body and a placement frame, a placement cavity and a heat preservation cavity are formed in the box body, and an opening is formed in the side face of the box body; the placing frame is slidably arranged on the top surface of the heat conducting plate, the tail end of the placing frame penetrates through the opening, fixing assemblies are arranged on the placing frame, baffles are arranged at the two adjacent fixing assemblies and the two ends of the placing frame, side plates and compression springs are arranged on the baffles, sealing strips are arranged on the side faces of the side plates, oblique angles are formed between the sealing strips and the edges of the side plates, and the sealing strips and the edges of the side plates are matched with the grooves; an auxiliary sealing group arranged at the opening is in contact with the baffle plate. Through the opening in the side face of the box body, the placing frame with the corresponding length can be pulled out when several semen samples are taken, the other semen samples are still located in the box body, and heat exchange is reduced; the opening is blocked through the baffle and the side plates, the auxiliary sealing set is matched, external air is prevented from entering the box body through the opening, the placing frame can be prevented from moving at will, and air convection can be reduced.
Owner:MOYU COUNTY BIBANG SHEEP IND DEV CO LTD

Semen specific mRNA-cSNP primer composition based on SNaPshot technology, kit and method

The invention discloses a seminal fluid specificity mRNA-cSNP primer composition based on an SNaPshot technology, a kit and a method, and belongs to the technical field of molecular identification. The primer composition provided by the invention comprises an amplification primer of which the nucleotide sequence is as shown in SEQ ID NO. 1 to 34 and a single-base extension primer of which the nucleotide sequence is as shown in SEQ ID NO. 35 to 52. The invention further provides a method for identifying the human semen sample. The method comprises the following steps: extracting mRNA of the sample, carrying out reverse transcription, obtaining cDNA, carrying out amplification reaction by using the amplification primer, and carrying out single-base extension reaction by using the single-base extension primer. Experimental results show that the identification method disclosed by the invention has the advantages of strong specificity, high sensitivity, good repeatability and the like, can be used for accurately identifying individual semen donors, and has important significance for realizing accurate semen-related criminal investigation and judicial expertise.
Owner:ACADEMY OF FORENSIC SCIENCE +1

Semen evaluation method and device based on lens-free imaging light intensity spatial and temporal distribution analysis

The invention discloses a sperm evaluation method and device based on lensless imaging light intensity spatial and temporal distribution analysis, and the method comprises the steps: carrying out lensless imaging continuous collection on a sperm sample, obtaining a lensless imaging time sequence, extracting a single-frame image from the lensless imaging time sequence, reconstructing the single-frame image, and obtaining a sperm evaluation result. Calculating the fractal dimension of a reconstructed image, evaluating the number of sperm individuals according to the fractal dimension, obtaining the sperm density in combination with the sample volume, extracting a pixel light intensity time sequence from the lens-free imaging time sequence, calculating the time correlation and spatial correlation of light intensity fluctuation, and obtaining the sperm density. And evaluating the sperm motility ability based on the temporal correlation and the spatial correlation. According to the invention, accurate, comprehensive, rapid, simple and convenient detection and evaluation on the animal sperm quality in the production field are realized.
Owner:JIANGSU POLYTECHNIC COLLEGE OF AGRI & FORESTRY

Sperm capturing device and sperm capturing method

The invention discloses a sperm capturing device and a sperm capturing method, and relates to the technical field of assisted reproduction equipment, the sperm capturing device comprises at least two chambers which are arranged in sequence, the chamber at the starting end is used for injecting a liquefied sperm sample, the other chambers are used for injecting a sperm washing liquid sample, and the sperm washing liquid sample is used for injecting a sperm washing liquid sample; the viscosity of the liquid sample in each chamber is sequentially reduced along the arrangement direction of each chamber; the at least one sorting membrane is correspondingly arranged between the two adjacent cavities, through holes distributed in an array mode are formed in the sorting membrane, the through holes are used for communicating the two cavities and allowing sperms to pass through, the two sides of the sorting membrane are immersed in the liquid samples on the two sides of the sorting membrane, and the sorting membrane is used for sorting and capturing the sperms under the fluid chemotaxis effect; and the damage to the sperms caused by repeated centrifugation in the traditional sperm treatment process is overcome.
Owner:JIANGSU MEDNOVO MEDICAL GRP CO LTD

Portable full-automatic fluorescence spectrum sperm activity detection method and system

The application provides a portable full-automatic fluorescence spectrum sperm activity detection method and system, and belongs to the technical field of sperm activity detection. The method comprises the following steps: placing a semen sample to be detected into a detection kit to which a sperm activity fluorescence biological dyeing agent is added; the sperm activity fluorescence biological dyeing agent comprises a CM-Dil biological derivative activation dyeing solution; fluorescence spectrum information of the semen sample to be detected is acquired through a far-field optical fluorescence microscope and a microscopic optical information acquisition assembly; the fluorescence spectrum information is subjected to data analysis through a spectrum analysis system, so as to obtain survival rate information, development state information and activity classification information of sperm in the semen sample. The application realizes that a person to be detected can complete sperm activity detection by himself without going to a hospital; and the detection result contains the survival rate information, the development state information and the activity classification information of sperm in the semen sample, so that whether the person to be detected has the ability to reproduce can be accurately determined.
Owner:SHANDONG NORMAL UNIV

Assisted reproduction information analysis method

The invention discloses an assisted reproduction information analysis method, and belongs to the technical field of assisted reproduction. After sperm extraction through masturbation of a patient, a sperm sample is transferred to a glass slide, sperm activity is observed through a microscope and classified, and a characteristic area is selected as a research object. And acquiring state characteristics of the sperms in the characteristic area, repeatedly measuring after different treatment courses of medicine taking, establishing a state change model, and calculating a state change value. And generating a state change curve by taking the state change value corresponding to each treatment course as a reference point, and judging the medicine taking effect by analyzing a derivative value of the curve. And when the absolute value of the derivative value tends to 0 for two continuous times and the tendency degree of the next time is higher, prompting that the drug efficacy is limited and the prescription needs to be replaced. The sperm state can be dynamically monitored and comprehensively analyzed, the classification accuracy is improved, the treatment effect is comprehensively evaluated, a doctor is helped to optimize a treatment scheme, and the scientificity and accuracy of assisted reproduction treatment are improved.
Owner:JILIN UNIV FIRST HOSPITAL

Methods for analyzing somatic cell-derived DNA molecules in a semen sample

PCT designated stageWO2025240773A1Microbiological testing/measurementDNA preparationSemen sampleAnalysis semen
Methods for analyzing somatic cell-derived DNA molecules in a semen sample. The methods may involve, individually or in combination, isolating and analyzing select populations of DNA obtained from sperm cells and somatic cells in a semen sample and size-based sorting. The methods further relate to quantitative analysis of somatic cell-derived DNA molecules in a semen sample. The methods described herein also relate to diagnostic methods for detecting prostate cancer, benign prostate hyperplasia (BPH), prostatitis, or testicular cancer in isolated populations of somatic cell-derived DNA obtained from a patient.
Owner:FELLOW HEALTH INC

Application of methyl nicotinate as marker in evaluation of bull semen quality

The invention discloses application of methyl nicotinate as a marker in evaluation of bull semen quality, and belongs to the technical field of animal reproduction and metabonomics. The relative content of methyl nicotinate in the bull rumen fluid with high semen quality is significantly higher than the relative content of methyl nicotinate in the bull rumen fluid with low semen quality. By detecting the relative content, the bull semen quality is evaluated, the reproductive performance can be reliably judged on the premise of not depending on a semen sample, and the method has the remarkable advantages of being non-invasive, high in throughput, capable of advancing a prediction window and the like.
Owner:INST OF ANIMAL SCI & VETERINARY MEDICINE SHANDONG ACADEMY OF AGRI SCI +1