Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia:The role of ambient temperature

Background:Paraplegia after spinal cord ischemia is a devastating condition in the clinic.Here,we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury.Methods:A total of 47 male rabbits were involved in the present study.Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures.To find the optimal conditions for developing delayed paraplegia,hindlimb motor function after ischemia was evaluated between experiments.Results:The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-i schemia period.More serious spinal cord injury occurred when ischemia was induced at higher temperatures.At 18°C,25-minute ischemia resulted in 74%of rabbits developing delayed paraplegia.At a temperature of 28°C or higher,most of the animals developed acute paraplegia immediately.While at 13°C,rabbits usually regained normal motor function without paraplegia.Conclusion:This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia.The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Methods to Reduce the Hypoglycemic Mortality of Alloxan in Diabetic Rabbit Model

Objective: To explore an intervention method to reduce the mortality of alloxan diabetes model, and to preliminarily analyze the mechanism of alloxan induced animal death. Methods: Healthy New Zealand rabbits were randomly divided into injection group, control group, experimental group and blank group. The single injection group was injected with 100 mg/kg alloxan once. The control group was given 5% glucose solution and 100 mg/kg alloxan was injected in two times. The experimental group was given 5% glucose solution orally, 100 mg/kg alloxan, 7 mL 0.9% NaCl intravenously and 5 mL 5% glucose intraperitoneally immediately, and blood glucose was continuously monitored, 10 mL 5% glucose intravenously and 10 mL 5% glucose intraperitoneally every 4 h in the hypoglycemic stage. The blank group does nothing. Liver and kidney tissues at different time periods were stained with HE and organ index was evaluated. Results: 1) A single injection of 100 mg/kg alloxan without any intervention resulted in 100% mortality. Before modeling, oral administration of 5% glucose solution, divided into two injections of 100 mg/kg alloxan, mortality reached 100%;A single injection of 100 mg/kg alloxan and continuous intervention of normal saline and glucose for 20 h can significantly reduce the mortality of alloxan induced diabetic rabbit model. 2) Liver and kidney tissues were damaged in different degrees at different time periods, and liver and kidney indexes were significantly increased after alloxan injection compared with the normal group, with statistical significance (P > 0.05). Conclusion: 1) Every 4 hours of hypoglycemia, 10 ml 5% glucose was injected intravenously 10 ml 5% glucose intraperitoneally. It can reduce the death rate of alloxan diabetic rabbit model and shorten the time of blood glucose measurement. 2) After the injection of alloxan, acute lesions of liver and kidney may occur in different degrees, or one of the causes of acute death of experimental animals.

Effects of histamine HlR-H4R-agonist on the airway epithelium of rabbits

Objective:To explore the exact role of histamine receptors in respiratory system.Methods: The cohort comprised of six groups(group I control and groupⅡ—Ⅳtreated) containing five rabbits in each group.Control-group received vehicle(sterile distilled water) and treated groups received subcutaneous histamine(100μg/kg,b.i.d.),and H1R-agonist(HTMT),H2R-agonist (amthamine),H3R-agonist(R-(-)-α-methylhistamine) and H4R-agonist(clobenpropit) each in a dose of 10μg/kg,b.i.d.for 30 subsequent days.After completion of treatment,animals were euthanized and perfused with 10% buffered formalin.Small tissue blocks of trachea and lungs were processed for paraffin embedding.Observations were recorded in sample photomicrographs taken from 10μm thick.Haematoxylin and eosin stained sections.Results:It was observed that trachea and bronchi from histamine,H1R and H4R groups had only patches of hyperplastic and hypertrophied epithelium and in general,cells in the affected region were taller heaped up. The bronchiolar epithelia from all treated groups showed hypertrophy and hyperplasia throughout with most of the cells having rounded profile and appeared to bud out from the basal cells. Conclusions:It is concluded that histamine receptors on induction via its specific agonist can induce hypertrophy,hyperplasia of respiratory tract epithelia suggesting its role akin to growth stimulating factor and warranting further long-term study.

A novel approach for 25-gauge transconjunctival sutureless vitrectomy to evaluate vitreous substitutes in rabbits

AIM:To improve the standard three-port vitrectomy for establishing and evaluating an endotamponade model in rabbits.METHODS:Three ports were prepared near the third eyelid of rabbits,and the infusion port was placed at the inferior nasal quadrant with the inserted cannula linking with a self-designed handheld rigid infusion catheter.All right eyes of rabbits underwent a modified 25-gauge vitrectomy and were subsequently filled with balanced salt solution,silicone oil,and eight-arm polyethylene glycols(8-arm PEGs)hydrogel separately for comparison.Ophthalmic examinations were performed regularly to record the changes after the surgery.RESULTS:Successful vitrectomy was achieved among 44 chinchilla rabbits.The mean operation time was 4.51±1.25min.Four eyes(9.1%)presented limited lens touch and two eyes(4.5%)showed retinal touch during surgery.Incision leakage was found in three eyes(6.8%)after surgery.There was no endophthalmitis,hemorrhage,or retinal detachment during the observation period and ophthalmic examinations after the implantation of vitreous substitutes.CONCLUSION:The modified technique of the standard vitrectomy applied in the endotamponade model in rabbits shows excellent safety and practicality.

Validation of a preclinical dry eye model in New Zealand white rabbits during and following topical instillation of 1% ophthalmic atropine sulfate

Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21,and 30(OAS group). A second group(n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were:Schirmer I test, tear break-up time(TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.Results : While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control( p < 0.001), and versus basal production( p < 0.001). TBUT showed statistically significant differences between groups(days 3 and 10;p = 0.001) and versus basal values(day 3;p < 0.001). Fluorescein staining showed a statistically significant difference(day 3;p = 0.001). The most frequent clinical finding was conjunctival hyperemia(76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation(86.7% minimal;13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference.Conclusions : The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention;it is not a viable model after OAS administration is suspended.

Comparison of emergency surgical cricothyroidotomy and percutaneous cricothyroidotomy by experienced airway providers in an obese,in vivo porcine hemorrhage airway model

Background: Emergency front-of-neck airway(eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate”(CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.Methods: Twelve pigs [(60.3±4.1) kg] were anesthetized and exposed to 25%–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy”(n=6) or scalpelbougie-tube technique “surgical cricothyroidotomy”(n=6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.Results: In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median(interquartile range, IQR) times to secure airway were 109(IQR 71–130) s and 298(IQR 128–360) s(P=0.0152), arterial blood saturation(SaO2) were 74.7(IQR 46.6–84.2)% and 7.9(IQR 4.1–15.6)%(P=0.0167), PaO_(2) were 7.0(IQR 4.7–7.7) kPa and 2.0(IQR 1.1–2.9) kPa(P=0.0667), and times of cardiac arrest(proxy survival) were 137–233 s, 190(IQR 143–229) s, from CICO. All six animals survived surgical cricothyroidotomy, and two of six(33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5(IQR 7.5–21.3), did not influence time to secure airway.Conclusions: eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.

Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model

AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

Experimental Study on the Repair Effect of Xianlinggubao Capsule on Osteoporotic Vertebral Compression Fracture in Rabbits

[Objectives]To observe the effect of Xianlinggubao Capsule on osteoporotic vertebral compression fracture(OVCF)in rabbits and the influence mechanism of the repair of fractures.[Methods]Female June age 30 rabbits were randomly divided into control group,model control group and Xianlinggubao group.After bilateral ovariectomy,the model control group and Xianlinggubao group were injected with dexamethasone continuously for 4 weeks,and then the OVCF compound model was established by surgery.The Xianlinggubao group was treated with Xianlinggubao at a dose of 300 mg/(kg·d)for 60 d,while the blank control group and the model control group were treated with the same amount of normal saline for 60 d.The number of blood vessels and the expression of bone morphogenetic protein-2(BMP-2)were detected by immunohistochemical staining and the bone mineral density(BMD)in the callus of the third lumbar fracture area of rabbits was measured.The content of serum phosphorus(P),alkaline phosphatase(ALP)and total calcium(TCa)in rabbit venous blood were measured by automatic biochemical analyzer.The content of vascular endothelial growth factor(VEGF)and platelet-derived growth factor(PDGF)in rabbit venous blood were measured by ELISA kit.[Results]The number of blood vessels and the expression of BMP-2 in the callus of the third lumbar fracture area of rabbits was high in Xianlinggubao group,the content of serum P,ALP,TCa,VEGF and PDGF was obviously increased,BMD was obviously increased,the bone microstructure of the third lumbar vertebrae fracture area of rabbits was basically restored.Compared with the model control group(P<0.05),the difference was statistically significant.[Conclusions]Xianlinggubao Capsule can increase calcium and phosphorus deposition,promote the formation of blood vessels in the fracture area of OVCF in rabbits,and have a strong repair effect on OVCF in rabbits.

Propofol Target-Controlled Infusion Modeling in Rabbits:Pharmacokinetic and Pharmacodynamic Analysis

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

Factors influencing the continuity of evidence-based practice in perioperative airway management for elderly patients with fractures:A qualitative study

BACKGROUND More and more evidence-based practices are emerging,but researchers mostly focus on short-term effects,resulting in evidence-based practices not being applied in the clinic in the long term.In this study,we took the evidence-based practice of perioperative airway management in elderly fracture patients as an example and adopted a descriptive phenomenological approach to understand the influencing factors of its sustainability to provide a reference basis for promoting the continuity of evidence-based practice in the clinic.AIM To explore factors influencing the persistence of evidence-based practice in perioperative airway management in elderly patients with fractures.METHODS This study was qualitative research.Nine nurses who implemented evidencebased practice in the orthopedic ward of a tertiary comprehensive hospital in Shanghai from September 2023 to October 2023 were selected using purposive sampling as research subjects.Semi-structured interviews were conducted with them,and the data were analyzed using the Colaizzi phenomenological analysis method based on the three dimensions and ten factors of the NHS sustainability model.RESULTS Three main themes and ten subthemes were identified:Process aspects(benefits to patients,benefits to nurses,lack of follow-up,complex processes);staff aspects(insufficient human resources,inadequate training and education,lack of leadership support);and organizational environment aspects(inadequate infrastructure,poor patient compliance,poor doctor cooperation).CONCLUSION Human resources,training and education,leadership support,infrastructure,and patient-physician collaboration are important factors influencing the sustainability of evidence-based practice for perioperative airway management in older patients with fractures.

A New Model of Experimental Cerebral Infarction in New Zealand White Rabbits

To develop an easy, reproducible experimental model of cerebral infarction(CI)without craniotomy in New Zealand white rabbits,a silicone rubber cylinder embedded in a nylon suture was delivered to the middle cerebral arteries through the internal carotid artery in anesthetized animals.Rabbits were sacrificed 0.5-5 h after embolization.CI size and location were ascertained by the tripheny1-2H-tetrazoliuni chloride(TTC)staining method;cerebral blood flow(CBF)was measured prior to and after embolization.Pco2,temperature and blood pressure were monitored and kept constant.CI occurred in all rabbits after 4 h of ischemia,in 50% after 3 h and only in 33% after 2.5 h.CI did not occur within less than 2.5 h of ischemia.No correlation was found between size and location of CI and occlusion time.CBF was maximally reduced in the right MCA territory but was also reduced in both anterior cerebral arteries and left MCA territories.This model is technically easy and the retrievable embolus allows the study of reperfusion by pulling on the nylon suture.It is suitable for studying chemical and molecular changes of the ischemic cells and/or for studying neuroimage changes after ischemic stroke.

Development and characterization of urethral stricture model in rabbits

Objective： To establish an experimental model of urethral stricture in rabbits. Methods： A total of 21 adult male New Zealand rabbits were included into group. After intravenous anesthesia, urethroscopy was performed with a pediatric resectoscope （F13）. Fifteen animals were randomly selected as the study group. A lcm-long circumferential electrocoagulation of the bulbar urethra was performed to these animals until ulceration of the mucosa. The remaining 6 animals underwent video urethroscopy without electrocoagulation, serving as controls. On the 30th day, retrograde urethrogram and urethroscopy were performed to evaluate urethral stricture formation, histological examinations （HE and Sirius Red staining） were done to assess urethral pathological change. Results： Two rabbits in study group died and no death occurred in controls. Based on urethrogram and urethroscopy, no rabbits in control group developed urethral stricture, while significant stricture formation was observed in every case of the study group. Histological examination showed a normal urethra in control cases, while at stricture site of the study group extensive fibrosis of muscle and submucous tis High collagen expression in fibrosis tissue was assayed sue by was observed with a large number of fibroblasts infiltration Sirius Red staining. Conclusion： A lcm-long endoscopic electrocoagulation can successfully induce urethral stricture formation in rabbit models. This method offers an ideal animal model for the fundamental and clinical study of urethral stricture

Clinical and pathological characteristics and expression of related molecules in patients with airway disseminated lung adenocarcinoma

Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.

Pharmacokinetics of Native r-SAK in Rabbit's Femoral Artery Thrombosis Model

Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.

Rabbit model of radiation-induced lung injury

Objective:To explore the feasibility of establishing an animal model of chronic radiationinduced lung injury.Methods:Twenty-eight New Zealand white rabbits were randomly divided into 3 groups(the right lung irradiation group,the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established b) highdoes radiotherapy in the irradiation groups,then all rabbits underwent CT and pathological examinations at 1.2.4.8.12.16 weeks,respectively after radiation.Results:Within 4 weeks of irradiation,some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At 8-12 weeks after irradiation,CT scanning showed ground glass samples signs,patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

Experimental and finite element analysis of tibial stress fractures using a rabbit model

AIM: To determine if rabbit models can be used to quantify the mechanical behaviour involved in tibial stress fracture(TSF) development.METHODS: Fresh rabbit tibiae were loaded under compression using a specifically-designed test apparatus. Weights were incrementally added up to a load of 30 kg and the mechanical behaviour of the tibia was analysed using tests for buckling, bone strain and hysteresis. Structural mechanics equations were subsequently employed to verify that the results were within the range of values predicted by theory. A finite element(FE) model was developed using cross-sectional computer tomography(CT) images scanned from one of the rabbit bones, and a static load of 6 kg(1.5 times the rabbit's body weight) was applied to represent running. The model was validated using the experimental strain gauge data, then geometric and elemental convergence tests were performed in order to find the minimum number of cross-sectional scans and elements respectively required for convergence. The analysis was then performed using both the model and the experimental results to investigate the mechanical behaviour of the rabbit tibia under compressive load and to examine crack initiation.RESULTS: The experimental tests showed that un der a compressive load of up to 12 kg, the rabbit tibia demonstrates linear behaviour with little hysteresis Up to 30 kg, the bone does not fail by elastic buckling however, there are low levels of tensile stress which predominately occur at and adjacent to the anterio border of the tibial midshaft: this suggests that fatigue failure occurs in these regions, since bone under cycli loading initially fails in tension. The FE model predic tions were consistent with both mechanics theory and the strain gauge results. The model was highly sensi tive to small changes in the position of the applied load due to the high slenderness ratio of the rabbit s tibia. The modelling technique used in the curren study could have applications in the development o human FE models of bone, where, unlike rabbit tibia the model would be relatively insensitive to very sma changes in load position. However, the rabbit mode itself is less beneficial as a tool to understand the me chanical behaviour of TSFs in humans due to the sma size of the rabbit bone and the limitations of human scale CT scanning equipment.CONCLUSION: The current modelling technique could be used to develop human FE models. However, the rabbit model itself has significant limitations in under standing human TSF mechanics.

Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

AIM： To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS： A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography （CT） and magnetic resonance imaging （MRI） were used to observe tumorgrowth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded.RESULTS： Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density loci of the tumor in the rectum wail, while enhanced CT scanning demonstrated a symmetrical intensification in tumor loci. MRI scanning showed alow signal of the tumor on T1-weighted imaging anda high signal of the tumor on T2-weighted imaging.Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could beobserved 6 wk after VX2 cell implantation, and a largearea of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation.CONCLUSION： The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.

Establishment of a chronic left ventricular aneurysm model in rabbit

Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm （LVA） in rabbits. Methods Acute myocardial infarction （AMI） was induced in 35 rabbits via concomitant ligation of the left anterior descending （LAD） coronary artery and the circumflex （Cx） branch at the middle portion. Development of AMI was co n-firmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar i n-tra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure （LVESP） and diastolic pressure （LVEDP） were measured before, immediately after and four weeks after ligation. D i-mensions of the ventricular chamber, thickness of the interventricular septum （IVS） and the left ventricular posterior wall （LVPW） left ventricular end diastolic volume （LVEDV） and systolic volume （LVESV）, and ejection fraction （EF） were recorded by echo-cardiography. Results Thirty one （88.6%） rabbits survived myocardial infarction and 26 of them developed aneurysm （83.9%）. The mean area of aneurysm was 33.4% ＆#177; 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the left ventricle （LV） that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce develo pment of LVA at a mean area ratio of 33.4%＆#177;2.4%which involves the apex, anterior wall and lateral wall of the LV.

Comparison of two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma

AIM:To compare two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma.METHODS:Thirty New Zealand rabbits were randomly divided into two groups:A and B.Group A was assigned a traditional laparotomy method(embedding tumor fragments directly into the liver with tweezers).Group B was subjected to an improved laparotomy method(injection of tumor fragments into the liver through a 15 G syringe needle).The operation time, incision length, incision infection rate, and mortality rate were compared between the two groups after laparotomy.Magnetic resonance imaging(MRI) was performed to evaluate tumor formation rates and the characteristics of the tumors 2 wk after laparotomy.RESULTS:The mean operation times for the two groups(Group A vs Group B) were 23.2 ± 3.4 min vs 17.5 ± 2.9 min(P < 0.05); the incision length was 3.3 ± 0.5 cm vs 2.4 ± 0.6 cm(P < 0.05); and the mortality rate after 2 wk was 26.7% vs 0%(P < 0.05); all of these outcomes were significantly different between the two groups.The incision infection rates in the two groups were 6.7% vs 0%(P > 0.05), whichwere not significantly different.MRI performed after 2weeks showed that the tumor formation rates in the two groups were 90.9%vs 93.3%(P>0.05).These rates were not significantly different between the two groups.The celiac implantation rate and abdominal wall metastasis rate in the two groups were 36.4%vs 13.3%(P<0.05)and 27.2%vs 6.7%(P<0.05),respectively,which were significantly different between the two groups.CONCLUSION:The tumor formation rates were not significantly different between the two methods for modeling rabbit VX2 hepatocarcinoma.However,the improved method is recommended because it has certain advantages.