Objective:To conduct a survey on the influence of personality trait on depres-sive symptom and obesity in patients before bariatric and metabolic surgery.Methods:The retros-pective cross-sectional investigation study was conducted. Patients who underwent bariatric and metabolic surgery in The Third Xiangya Hospital of Central South University and The First Affiliated Hospital of Ji′nan University from January 1 to June 1,2024 were recruited. The survey was conducted in electronic format using the general information survey questionnaire, the patient health question-naire-9 (PHQ-9), and the Chinese big five personality inventory brief version (CBF-PI-B). Observa-tion indicators: (1) results of the questionnaire; (2) general data of patient; (3) personality trait scores for patient with different subtypes of obesity; (4) depression symptom scores for patient with different subtypes of obesity; (5) correlation analysis for patient personality trait, depressive symptom and body mass index (BMI). Comparison of measurement data with normal distribution between groups was conducted using the independent t test, and one-way analysis of variance was used for comparison among multiple groups. LSD test was used for pairwise comparison. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test, and Dunn Bonferroni test was used for pairwise comparison. The Spearman correlation analysis and Pearson correlation analysis were used for correlation analysis, and the mediation effect analysis was conducted using the Process 4.0 model and the Bootstrap test. Results:(1)Results of the questionnaire. A total of 146 questionnaires were distributed and collected, including 83 questionnaires from The Third Xiangya Hospital of Central South University and 63 questionnaires from The First Affiliated Hospital of Ji′nan University. Of 146 questionnaires, 137 questionnaires were valid, yielding an effective response rate of 93.836%(137/146). (2)General data of patient. Of the 137 patients who completed valid questionnaires, 52 were male with BMI of (41±5)kg/m 2, 85 were female with BMI of (38±6)kg/m 2, showing a significant difference between them ( t=2.586, P<0.05). There were 40 patients aged ≤25 years, with BMI of (42±5)kg/m 2, 28 patients aged 26-30 years, with BMI of (39±5)kg/m 2, 49 patients aged 31-40 years, with BMI of (38±6)kg/m 2, 14 patients aged 41-50 years, with BMI of (38±7)kg/m 2, 6 patients aged >50 years, with BMI of (37±3)kg/m 2. There were significant differences in BMI of patients of different age groups ( F=2.697, P<0.05). (3)Persona-lity trait scores for patient with different subtypes of obesity. Of the 137 patients who completed valid questionnaires, there were 15 patients of mild obesity, with personality trait neuroticism score of 19.0(14.0,24.0), personality trait strictness score of 32.5±5.2, personality trait extroversion score of 30.0(24.0,40.0), 36 patients of moderate obesity, with personality trait neuro-ticism score of 26.5(22.3,28.8), personality trait strictness score of 32.6±5.9, personality trait extro-version score of 34.0(26.3,39.0), 81 patients of severe obesity, with personality trait neuroticism score of 35.0(29.5,41.0), personality trait strictness score of 26.8±7.4, personality trait extroversion score of 28.0(20.5,35.0), 5 patients of extreme obesity, with personality trait neuroticism score of 28.0(26.5,44.0), personality trait strictness score of 19.6±3.4, personality trait extroversion score of 22.0(18.5,25.0). There were significant differences in personality trait neuroticism, strictness and extroversion among patients of different subtypes of obesity ( H=50.316, F=10.774, H=14.446, P<0.05). (4)Depression symptom scores for patient with different subtypes of obesity. Of the 137 pati-ents who completed valid questionnaires, the depressive symptom score were 4.0(2.0,9.0) for 15 pati-ents of mild obesity, 5.0(3.0,7.0) for 36 patients of moderate obesity, 13.0(8.5,17.0) for 81 patients of severe obesity, and 18.0(9.5,22.0) for 5 patients of extreme obesity, respectively, showing a significant difference among them ( H=50.129, P<0.05). (5) Correlation analysis for patient personality trait, depressive symptom and BMI. Results of Spearman correlation analysis showed that personality trait neuroticism were positively correlated with depressive symptoms and BMI ( r=0.780, 0.557, P<0.05), personality trait strictness was negatively correlated with depressive symptoms ( r=-0.523, P<0.05), personality trait extroversion were negatively correlated with depressive symptoms and BMI ( r=-0.448, -0.323, P<0.05), and depressive symptoms was positively correlated with BMI ( r=0.568, P<0.05). Results of Pearson correlation analysis showed that personality trait strictness was negatively correlated with BMI ( r=-0.489, P<0.05). Conclusion:Preoperative personality trait of patients undergoing bariatric and metabolic surgery can influence their depressive symptom and BMI.

Objective:To investigate the effect of ERMAP on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its related mechanism.Methods:The experimental mice were divided into 3 groups:Sham group,WT group and ERMAP-/-group,with 9 mice in each group.The Sham group was smeared with Vaseline,and the WT group and ERMAP-/-group were smeared with IMQ to induce psoriatic dermatitis.The severity of IMQ-induced psoriasis lesions in mice were evaluated according to the psoria-sis area and severity index(PASI)and the HE staining pathology score.The expressions of F4/80 and Ki67 in mouse skin lesions were observed by immunofluorescence staining.The relative expressions of IL-1β,IL-6,IFN-γ and iNOS in skin lesions were detected by qRT-PCR.Flow cytometry was used to detect the proliferation and activation of T cells and the proportion of macrophages in spleen.Results:In the IMQ-induced mouse model of psoriasis-like dermatitis,the skin lesions of ERMAP gene knock out mice showed more severe squamous accumulation and skin bulge,more inflammatory cells aggregation and cytokine production,and the proportion of immune cells in the spleen of mice increased compared with the WT group,and the proportion of M1 macrophages increased.Conclu-sion:ERMAP deficiency aggravates IMQ-induced psoriasis-like skin inflammation in mice by enhancing immune response.

BACKGROUND:In most species,a bone defect that is longer than 1.5 or 2 times its diameter can be considered a critical bone defect,and when the bone defect volume reaches the critical value,it cannot heal on its own.Currently,there is no uniform standard for the size of critical-sized defects in the osteoporotic femoral condyle of rabbits.OBJECTIVE:To establish a rabbit model with different sizes of bone defects in the osteoporotic femoral condyle and to determine the critical-sized defects of osteoporotic femoral condyle in rabbits.METHODS:Thirty-six 3-month-old female New Zealand white rabbits were randomly divided into ovariectomy group(n=30)and sham operation group(n=6).Rabbits in the ovariectomy group underwent bilateral ovariectomy to establish an osteoporosis model,and then femoral condyle bone defect models of different diameters(diameters were 4,5,6,and 7 mm,and depths were 8 mm)were further established;rabbits in the sham operation group did not undergo ovariectomy.At 8 and 12 weeks after modeling,3 rats were randomly selected from each group for CT scanning and three-dimensional reconstruction to evaluate the healing of bone defects.Afterwards,samples were taken for gross observation and hematoxylin-eosin staining to observe the growth of new bone in the femoral condyle bone defect area.RESULTS AND CONCLUSION:(1)All rabbits survived and moved well after modeling of osteoporosis and femoral condyle bone defect.(2)At 12 weeks after osteoporosis modeling,dual-energy X-ray absorptiometry results showed that the bone mineral density of lumbar vertebrae in ovariectomy group was significantly lower than that in sham operation group(P＜0.05).Hematoxylin-eosin staining showed that the bone trabeculae in the ovariectomy group became thinner and sparse.The proportion of bone tissue area in the ovariectomy group was significantly lower than that in the sham operation group(P=0.00).Micro-CT results showed that the bone tissue parameters of the femoral condyle in the ovariectomy group were significantly different from those in the sham operation group(P＜0.05),and the ovariectomy group showed obvious characteristics of osteoporosis.(3)CT showed that the bone defect in the 4 mm and 5 mm diameter groups was basically completely repaired at 12 weeks after surgery.There was more new bone tissue in the 6 mm diameter group,but the central part of the bone defect was not completely repaired.A small amount of new bone tissue grew in the 7 mm diameter group,and the bone defect was obvious.(4)Gross observation at 12 weeks after surgery showed that the femoral condyle bone defect in the 4 mm and 5 mm diameter groups was completely repaired.Obvious depression was seen in the bone defect area of the 6 mm and 7 mm diameter groups,and the bone defect was not completely repaired.(5)Histological observation at 12 weeks after surgery showed that the bone defect area of the 4 mm and 5 mm diameter groups was completely filled with new bone,and the trabecular structure was irregular;while there were new trabeculae in the periphery of the 6 mm and 7 mm diameter groups,and the bone defect in the central area was still obvious.(6)The results showed that during the 12-week experimental observation period of osteoporotic femoral condyle defects in rabbits,under the condition of the same defect depth of 8 mm,femoral condyle defects with a diameter ≥ 6 mm could not heal on their own,while femoral condyle defects with a diameter＜6 mm were completely repaired.A diameter of 6 mm and a depth of 8 mm can be used as the critical bone defect value of osteoporotic femoral condyle in rabbits.

Objective:To investigate the effect of ERMAP on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its related mechanism.Methods:The experimental mice were divided into 3 groups:Sham group,WT group and ERMAP-/-group,with 9 mice in each group.The Sham group was smeared with Vaseline,and the WT group and ERMAP-/-group were smeared with IMQ to induce psoriatic dermatitis.The severity of IMQ-induced psoriasis lesions in mice were evaluated according to the psoria-sis area and severity index(PASI)and the HE staining pathology score.The expressions of F4/80 and Ki67 in mouse skin lesions were observed by immunofluorescence staining.The relative expressions of IL-1β,IL-6,IFN-γ and iNOS in skin lesions were detected by qRT-PCR.Flow cytometry was used to detect the proliferation and activation of T cells and the proportion of macrophages in spleen.Results:In the IMQ-induced mouse model of psoriasis-like dermatitis,the skin lesions of ERMAP gene knock out mice showed more severe squamous accumulation and skin bulge,more inflammatory cells aggregation and cytokine production,and the proportion of immune cells in the spleen of mice increased compared with the WT group,and the proportion of M1 macrophages increased.Conclu-sion:ERMAP deficiency aggravates IMQ-induced psoriasis-like skin inflammation in mice by enhancing immune response.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

To investigate the association between obesity-related metabolic indices and the risk of knee osteoarthritis(KOA) in middle-aged and older Chinese adults(≥45 years) using data from the China Health and Retirement Longitudinal Study(CHARLS).

Objective:To conduct a survey on the influence of personality trait on depres-sive symptom and obesity in patients before bariatric and metabolic surgery.Methods:The retros-pective cross-sectional investigation study was conducted. Patients who underwent bariatric and metabolic surgery in The Third Xiangya Hospital of Central South University and The First Affiliated Hospital of Ji′nan University from January 1 to June 1,2024 were recruited. The survey was conducted in electronic format using the general information survey questionnaire, the patient health question-naire-9 (PHQ-9), and the Chinese big five personality inventory brief version (CBF-PI-B). Observa-tion indicators: (1) results of the questionnaire; (2) general data of patient; (3) personality trait scores for patient with different subtypes of obesity; (4) depression symptom scores for patient with different subtypes of obesity; (5) correlation analysis for patient personality trait, depressive symptom and body mass index (BMI). Comparison of measurement data with normal distribution between groups was conducted using the independent t test, and one-way analysis of variance was used for comparison among multiple groups. LSD test was used for pairwise comparison. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test, and Dunn Bonferroni test was used for pairwise comparison. The Spearman correlation analysis and Pearson correlation analysis were used for correlation analysis, and the mediation effect analysis was conducted using the Process 4.0 model and the Bootstrap test. Results:(1)Results of the questionnaire. A total of 146 questionnaires were distributed and collected, including 83 questionnaires from The Third Xiangya Hospital of Central South University and 63 questionnaires from The First Affiliated Hospital of Ji′nan University. Of 146 questionnaires, 137 questionnaires were valid, yielding an effective response rate of 93.836%(137/146). (2)General data of patient. Of the 137 patients who completed valid questionnaires, 52 were male with BMI of (41±5)kg/m 2, 85 were female with BMI of (38±6)kg/m 2, showing a significant difference between them ( t=2.586, P<0.05). There were 40 patients aged ≤25 years, with BMI of (42±5)kg/m 2, 28 patients aged 26-30 years, with BMI of (39±5)kg/m 2, 49 patients aged 31-40 years, with BMI of (38±6)kg/m 2, 14 patients aged 41-50 years, with BMI of (38±7)kg/m 2, 6 patients aged >50 years, with BMI of (37±3)kg/m 2. There were significant differences in BMI of patients of different age groups ( F=2.697, P<0.05). (3)Persona-lity trait scores for patient with different subtypes of obesity. Of the 137 patients who completed valid questionnaires, there were 15 patients of mild obesity, with personality trait neuroticism score of 19.0(14.0,24.0), personality trait strictness score of 32.5±5.2, personality trait extroversion score of 30.0(24.0,40.0), 36 patients of moderate obesity, with personality trait neuro-ticism score of 26.5(22.3,28.8), personality trait strictness score of 32.6±5.9, personality trait extro-version score of 34.0(26.3,39.0), 81 patients of severe obesity, with personality trait neuroticism score of 35.0(29.5,41.0), personality trait strictness score of 26.8±7.4, personality trait extroversion score of 28.0(20.5,35.0), 5 patients of extreme obesity, with personality trait neuroticism score of 28.0(26.5,44.0), personality trait strictness score of 19.6±3.4, personality trait extroversion score of 22.0(18.5,25.0). There were significant differences in personality trait neuroticism, strictness and extroversion among patients of different subtypes of obesity ( H=50.316, F=10.774, H=14.446, P<0.05). (4)Depression symptom scores for patient with different subtypes of obesity. Of the 137 pati-ents who completed valid questionnaires, the depressive symptom score were 4.0(2.0,9.0) for 15 pati-ents of mild obesity, 5.0(3.0,7.0) for 36 patients of moderate obesity, 13.0(8.5,17.0) for 81 patients of severe obesity, and 18.0(9.5,22.0) for 5 patients of extreme obesity, respectively, showing a significant difference among them ( H=50.129, P<0.05). (5) Correlation analysis for patient personality trait, depressive symptom and BMI. Results of Spearman correlation analysis showed that personality trait neuroticism were positively correlated with depressive symptoms and BMI ( r=0.780, 0.557, P<0.05), personality trait strictness was negatively correlated with depressive symptoms ( r=-0.523, P<0.05), personality trait extroversion were negatively correlated with depressive symptoms and BMI ( r=-0.448, -0.323, P<0.05), and depressive symptoms was positively correlated with BMI ( r=0.568, P<0.05). Results of Pearson correlation analysis showed that personality trait strictness was negatively correlated with BMI ( r=-0.489, P<0.05). Conclusion:Preoperative personality trait of patients undergoing bariatric and metabolic surgery can influence their depressive symptom and BMI.

Objective To investigate the potential profile of self-management behavior in patients with sudden deafness,the characteristics and influencing factors of different categories of patients,and provide reference for clin-ical management.Methods A total of 205 patients with sudden deafness who were hospitalized in the Department of Otology of a Grade 3 hospital in Beijing were selected by convenience sampling method from August 2023 to June 2024.Date were collected using the general situation questionnaire,self-management status assessment scale for sudden deafness patient and social support rating scale.Mplus 8.0 was used for potential profile analysis,and SPSS 26.0 was used for single factor analysis and multiple logistic regression analysis.Results A total of 200 valid ques-tionnaires were collected.Patients were divided into 3 categories according to their self-management level,which were respectively named as"high management—good self-efficacy group"(n=52,26.00％),"moderate manage-ment—symptoms of special concern group"(n=101,50.50％),and"low management-lack of information acquisi-tion group"(n=47,23.50％).Multiple logistic regression analysis showed that education level,sleep disorder and social support level were the influencing factors of different self-management categories in patients with sudden deaf-ness.Conclusion The overall self-management ability of patients with sudden deafness is at a moderate level and with significant heterogeneity.Education level,sleep disorders,and social support serve as stratification criteria for categorizing different patient groups and formulating corresponding intervention strategies.Priority should be given to providing information support to the"low-management group with information deficiency",implementing targe-ted interventions for the"moderate-management group with symptom focus",and fully leveraging the self-efficacy of the"high-management group with good self-efficacy"to regulate their self-management level.

BACKGROUND:In most species,a bone defect that is longer than 1.5 or 2 times its diameter can be considered a critical bone defect,and when the bone defect volume reaches the critical value,it cannot heal on its own.Currently,there is no uniform standard for the size of critical-sized defects in the osteoporotic femoral condyle of rabbits.OBJECTIVE:To establish a rabbit model with different sizes of bone defects in the osteoporotic femoral condyle and to determine the critical-sized defects of osteoporotic femoral condyle in rabbits.METHODS:Thirty-six 3-month-old female New Zealand white rabbits were randomly divided into ovariectomy group(n=30)and sham operation group(n=6).Rabbits in the ovariectomy group underwent bilateral ovariectomy to establish an osteoporosis model,and then femoral condyle bone defect models of different diameters(diameters were 4,5,6,and 7 mm,and depths were 8 mm)were further established;rabbits in the sham operation group did not undergo ovariectomy.At 8 and 12 weeks after modeling,3 rats were randomly selected from each group for CT scanning and three-dimensional reconstruction to evaluate the healing of bone defects.Afterwards,samples were taken for gross observation and hematoxylin-eosin staining to observe the growth of new bone in the femoral condyle bone defect area.RESULTS AND CONCLUSION:(1)All rabbits survived and moved well after modeling of osteoporosis and femoral condyle bone defect.(2)At 12 weeks after osteoporosis modeling,dual-energy X-ray absorptiometry results showed that the bone mineral density of lumbar vertebrae in ovariectomy group was significantly lower than that in sham operation group(P＜0.05).Hematoxylin-eosin staining showed that the bone trabeculae in the ovariectomy group became thinner and sparse.The proportion of bone tissue area in the ovariectomy group was significantly lower than that in the sham operation group(P=0.00).Micro-CT results showed that the bone tissue parameters of the femoral condyle in the ovariectomy group were significantly different from those in the sham operation group(P＜0.05),and the ovariectomy group showed obvious characteristics of osteoporosis.(3)CT showed that the bone defect in the 4 mm and 5 mm diameter groups was basically completely repaired at 12 weeks after surgery.There was more new bone tissue in the 6 mm diameter group,but the central part of the bone defect was not completely repaired.A small amount of new bone tissue grew in the 7 mm diameter group,and the bone defect was obvious.(4)Gross observation at 12 weeks after surgery showed that the femoral condyle bone defect in the 4 mm and 5 mm diameter groups was completely repaired.Obvious depression was seen in the bone defect area of the 6 mm and 7 mm diameter groups,and the bone defect was not completely repaired.(5)Histological observation at 12 weeks after surgery showed that the bone defect area of the 4 mm and 5 mm diameter groups was completely filled with new bone,and the trabecular structure was irregular;while there were new trabeculae in the periphery of the 6 mm and 7 mm diameter groups,and the bone defect in the central area was still obvious.(6)The results showed that during the 12-week experimental observation period of osteoporotic femoral condyle defects in rabbits,under the condition of the same defect depth of 8 mm,femoral condyle defects with a diameter ≥ 6 mm could not heal on their own,while femoral condyle defects with a diameter＜6 mm were completely repaired.A diameter of 6 mm and a depth of 8 mm can be used as the critical bone defect value of osteoporotic femoral condyle in rabbits.