Current Situation and Progress of Pig Model in Otology Research

Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. This article introduces the applications, current status, progress, advantages, and issues of using pigs as otologic animal models. It summarizes current research on pigs in the fields of hearing disorders, otitis, vertigo, cochlea, gene editing, and tissue engineering, among other otologic and audiological areas. These models are valuable for translating basic medical science into clinical applications. Based on this, platforms have been established for studying deafness and vertigo, cochlear implantation experiments, stem cell and gene therapy, and tissue engineering. These serve as ideal experimental models for the prevention and treatment of ear diseases, pointing toward new directions. This will bolster the promotion and application of pig models in the fields of tissue engineering and gene editing in the future.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Improved methodology for efficient establishment of the myocardial ischemia-reperfusion model in pigs through the median thoracic incision

To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.

The impact of genotyping strategies and statistical models on accuracy of genomic prediction for survival in pigs

Background:Survival from birth to slaughter is an important economic trait in commercial pig productions.Increasing survival can improve both economic efficiency and animal welfare.The aim of this study is to explore the impact of genotyping strategies and statistical models on the accuracy of genomic prediction for survival in pigs during the total growing period from birth to slaughter.Results:We simulated pig populations with different direct and maternal heritabilities and used a linear mixed model,a logit model,and a probit model to predict genomic breeding values of pig survival based on data of individual survival records with binary outcomes(0,1).The results show that in the case of only alive animals having genotype data,unbiased genomic predictions can be achieved when using variances estimated from pedigreebased model.Models using genomic information achieved up to 59.2%higher accuracy of estimated breeding value compared to pedigree-based model,dependent on genotyping scenarios.The scenario of genotyping all individuals,both dead and alive individuals,obtained the highest accuracy.When an equal number of individuals(80%)were genotyped,random sample of individuals with genotypes achieved higher accuracy than only alive individuals with genotypes.The linear model,logit model and probit model achieved similar accuracy.Conclusions:Our conclusion is that genomic prediction of pig survival is feasible in the situation that only alive pigs have genotypes,but genomic information of dead individuals can increase accuracy of genomic prediction by 2.06%to 6.04%.

A combined pig model to determine the net absorption of volatile fatty acids in the large intestine under different levels of crude fiber

Background:This study aimed to develop a combined model to quantify the net absorption of volatile fatty acids(VFA)in the large intestine(LI)of pigs.Methods:Fifteen female growing pigs(Duroc×Large White×Landrace)were ranked by body weight(30±2.1 kg)on day 0 and assigned to one of three treatments,namely the basal diet containing different crude fiber(CF)levels(LCF:3.0%CF,MCF:4.5%CF,and HCF:6.0%CF).The pigs were implanted with the terminal ileum fistula and the cannulation of the ileal mesenteric vein(IMV),portal vein(PV),and left femoral artery(LFA)from days 6 to 7.[13 C]-Labeled VFA and P-aminohippuric acid were constantly perfused into the terminal ileum fistula and the cannulation of the IMV(day 15),respectively.Blood samples were collected from the PV and the LFA during perfusion(5 h),and LI samples were collected.Results:The net flux of[12 C]-acetic acid in the PV was greater for LCF versus MCF(p=0.045),but no difference was observed in the net flux of[12 C]-propionic acid(p=0.505)and[12 C]-butyric acid(p=0.35)in the PV among treatments.The deposition of[12 C]-acetic acid in the LI was greater for LCF versus MCF(p=0.014),whereas the deposition of[12 C]-propionic acid(p=0.007)and[12 C]-butyric acid(p=0.037)in the LI was greater for LCF versus HCF.Conclusions:In conclusion,this pig model was found conducive to study the net absorption of VFAs in the LI,and LCF had more net absorption of VFAs in the LI than MCF and HCF.

The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.

Dynamic changes of ocular biometric parameters:a modified form-deprivation myopia model of young guinea pigs

AIM: To evaluate the dynamic ocular biometric changes of a modified form-deprivation myopia model in young guinea pigs. METHODS: The animals were randomly assigned to two groups: the monocularly deprived facemask group (MDF, with all the right eyes covered, n=24) and the normal control group(free of facemask, n=24). Each group was then equally divided into four subgroups which were followed up for 2, 4, 6 and 8 weeks, respectively. Parameters measured from every eye included refraction, corneal curvature, axial length and the dry weight of sclera at the posterior pole. RESULTS: All the facemasks remained in place during the follow-up. The covered eyes developed myopia with the vitreous chamber lengthening and the dry weight of posterior sclera reduced at each time point compared with the contralateral uncovered (P<0.05 at all time points). The changes had a linear correlation with the deprivation time (P<0.05). There were no significant differences in all the parameters between the uncovered eyes of MDF group and the normal control group (P>0.05 at all time points). CONCLUSION: Monocular form deprivation with the facemask is highly effective and non-invasive in inducing axial myopia in guinea pigs. The axial myopia is mainly caused by the increased vitreous chamber length and the weakened posterior sclera rigidity. The form-deprivation eye didn't interfere with the natural development of the contralateral eye.

Advantages of a miniature pig model in research on human hereditary hearing loss

In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.

Dynamics of Advantageous Mutant Spread in Spatial Death-Birth and Birth-Death Moran Models

The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.

A new approach to endocochlear potential and potassium ion concentration measures in mini pig models

Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals.However,the study on porcine ears is still in the initial stage and there is no description of an ideal operation approach to endocochlear potential and potassium ion concentration measurements.In this article,we describe a pre-auricular surgical approach to access the middle and inner ear for endocochlear potential and potassium ion concentration measures in mini pig models.Ten one-week old normal mini pigs were used in the study.The bulla of the temporal bone was accessed via a pre-auricular approach for endocochlear potential and potassium ion concentration measurements.The condition of the animals during the first post—experiment 24 h was observed.One animal died during surgery.The preauricular approach improved protection and preservation of relevant nervous and vascular elements including the facial nerve and carotid artery.So,the pre-auricular approach can be used for endocochlear potential and potassium ion concentration measurements with improved nerve and artery preservation mini pigs.

Identification of predictive MRI and functional biomarkers in a pediatric piglet traumatic brain injury model

Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP: A2015 11-001) on December 22, 2015.

Development and characterization of a guinea pig model for Marburg virus

The Angolan strain of Marburg virus （MARV/Ang） can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice （MARV/Ang-MA）, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate （NHP） model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs （MARV/Ang- GA）. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 （median tissue culture infective dose）. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

Guinea pigs as an animal model for sciatic nerve injury

The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes.To address the problem,this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies.A crush injury was inflicted to the sciatic nerve of the left limb,which led to significant decrease in the pain perception and neurorecovery up to the 4th weak.Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury.A 3.49 ± 0.35 fold increase in expression of neuropilin 1（NRP1） gene and 2.09 ± 0.51 fold increase in neuropilin 2（NRP2） gene were recorded 1 week after nerve injury as compared to the normal nerve.Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30 th day.Histopathologically,vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers.Gastrocnemius muscle also showed degenerative changes.Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve.The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

Establishment of a male fertility prediction model with sperm RNA markers in pigs as a translational animal model

Background:Male infertility is an important issue that causes low production in the animal industry.To solve the male fertility crisis in the animal industry,the prediction of sperm quality is the most important step.Sperm RNA is the potential marker for male fertility prediction.We hypothesized that the expression of functional genes related to fertilization will be the best target for male fertility prediction markers.To investigate optimum male fertility prediction marker,we compared target genes expression level and a wide range of field data acquired from artificial insemination of boar semen.Results:Among the genes related to acrosomal vesicle exocytosis and sperm–oocyte fusion,equatorin(EQTN),zona pellucida sperm-binding protein 4(ZP4),and sperm acrosome membrane-associated protein 3 exhibited high accuracy(70%,90%,and 70%,respectively)as markers to evaluate male fertility.Combinations of EQTN-ZP4,ZP4-protein unc-13 homolog B,and ZP4-regulating synaptic membrane exocytosis protein 1(RIMS1)showed the highest prediction value,and all these markers are involved in the acrosome reaction.Conclusion:The EQTN-ZP4 model was efficient in clustering the high-fertility group and may be useful for selection of animal that has superior fertility in the livestock industry.Compared to the EQTN-ZP4 model,the ZP4-RIMS1 model was more efficient in clustering the low-fertility group and may be useful in the diagnosis of male infertility in humans and other animals.The appointed translational animal model and established biomarker combination can be widely used in various scientific fields such as biomedical science.

An integrative multivariate approach for predicting functional recovery using magnetic resonance imaging parameters in a translational pig ischemic stroke model

Magnetic resonance imaging(MRI)is a clinically relevant,real-time imaging modality that is frequently utilized to assess stroke type and severity.However,specific MRI biomarkers that can be used to predict long-term functional recovery are still a critical need.Consequently,the present study sought to examine the prognostic value of commonly utilized MRI parameters to predict functional outcomes in a porcine model of ischemic stroke.Stroke was induced via permanent middle cerebral artery occlusion.At 24 hours post-stroke,MRI analysis revealed focal ischemic lesions,decreased diffusivity,hemispheric swelling,and white matter degradation.Functional deficits including behavioral abnormalities in open field and novel object exploration as well as spatiotemporal gait impairments were observed at 4 weeks post-stroke.Gaussian graphical models identified specific MRI outputs and functional recovery variables,including white matter integrity and gait performance,that exhibited strong conditional dependencies.Canonical correlation analysis revealed a prognostic relationship between lesion volume and white matter integrity and novel object exploration and gait performance.Consequently,these analyses may also have the potential of predicting patient recovery at chronic time points as pigs and humans share many anatomical similarities(e.g.,white matter composition)that have proven to be critical in ischemic stroke pathophysiology.The study was approved by the University of Georgia(UGA)Institutional Animal Care and Use Committee(IACUC;Protocol Number:A2014-07-021-Y3-A11 and 2018-01-029-Y1-A5)on November 22,2017.

Leaf pigment retrieval using the PROSAIL model: Influence of uncertainty in prior canopy-structure information

Leaf pigments are critical indicators of plant photosynthesis,stress,and physiological conditions.Inversion of radiative transfer models(RTMs)is a promising method for robustly retrieving leaf biochem-ical traits from canopy observations,and adding prior information has been effective in alleviating the“ill-posed”problem,a major challenge in model inversion.Canopy structure parameters,such as leaf area index(LAI)and average leaf inclination angle(ALA),can serve as prior information for leaf pigment retrie-val.Using canopy spectra simulated from the PROSAIL model,we estimated the effects of uncertainty in LAI and ALA used as prior information for lookup table-based inversions of leaf chlorophyll(C _(ab))and car-otenoid(C_(ar)).The retrieval accuracies of the two pigments were increased by use of the priors of LAI(RMSE of C_(ab) from 7.67 to 6.32μg cm^(-2),C_(ar) from 2.41 to 2.28μg cm^(-2))and ALA(RMSE of C_(ab) from 7.67 to 5.72μg cm^(-2),C_(ar) from 2.41 to 2.23μg cm^(-2)).However,this improvement deteriorated with an increase of additive and multiplicative uncertainties,and when 40% and 20% noise was added to LAI and ALA respectively,these priors ceased to increase retrieval accuracy.Validation using an experimental winter wheat dataset also showed that compared with C_(ar),the estimation accuracy of C_(ab) increased more or deteriorated less with uncertainty in prior canopy structure.This study demonstrates possible limita-tions of using prior information in RTM inversions for retrieval of leaf biochemistry,when large uncer-tainties are present.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

The pig as a preclinical traumatic brain injury model:current models,functional outcome measures,and translational detection strategies

Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.

Technological Options to Ameliorate Waste Treatment of Intensive Pig Production in China:An Analysis Based on Bio-Economic Model

Ameliorating waste treatment by technological improvements affects the economic and the ecological-environment benefits of intensive pig production. The objective of the research was to develop and test a method to determine the technical optimization to ameliorate waste treatment methods and gain insight into the relationship between technological options and the economic and ecological effects. We developed an integrated bio-economic model which incorporates the farming production and waste disposal systems to simulate the impact of technological improvements in pig manure treatment on economic and environmental benefits for the case of a pilot farm in Beijing, China. Based on different waste treatment technology options, three scenarios are applied for the simulation analysis of the model. The simulation results reveal that the economic-environmental benefits of the livestock farm could be improved by reducing the cropland manure application and increasing the composting production with the current technologies. Nevertheless, the technical efficiency, the waste treatment capacity and the economic benefits could be further improved by the introduction of new technologies. It implies that technological and economic support policies should be implemented comprehensively on waste disposal and resource utilization to promote sustainable development in intensive livestock production in China.

Establishment of a pig model of combined pancreas-kidney transplantation

ＩＮＴＲＯＤＵＣＴＩＯＮＷｅｓｔｕｄｉｅｄｔｈｅｒｅｃｉｐｉｅｎｔａｎｄｇｒａｆｔｐａｔｈｏｐｈｙｓｉｏｌｏｇｉｃｃｈａｎｇｅｓａｆｔｅｒｔｒａｎｓｐｌａｎｔａｔｉｏｎ，ｔｈｅｉｎｄｕｃｅｍｅｎｔｏｆｉｍｍｕｎｏｔｏｌｅｒａｎｃｅ，ｔｈｅｒｅｇｕｌａ...