BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

Objective To study the effects of sensitized dendritic cells in the treatment of bladder tumor and further discuss the mechanism of this immunotherapy. Methods 44 female F344 rats, which irrigated N-methyl-N-nitrosourea into bladders every other week for a total of five doses, were induced to bladder tumor. They were treated subcutaneously with either PBS, unsensitized DC, freeze thawing supernatant of tumor cells, or sensitized DC respectively every week for a total of four times. In the fifteenth week, their bladders were weighted and harvested for observation by naked eye and microscope, their blood was harvested for examination CTL by FCM. Results The weight of bladders in sensitized DC group was lower than those in PBS group, unsensitized DC group and freeze thawing supernatant of bladder tumor cells group (P<0.05). The stages of bladder tumor in sensitized DC group were statistically descended compared with those in PBS group (P <0.05). The CD+3 T cells in sensitized DC group was lower than those in PBS group, unsensitized DC group and freeze thawing supernatant of bladder tumor cells group (P <0.05). The CD+3 CD+8 CD+28 T cells in sensitized DC group was higher than those in PBS group, unsensitized DC group and freeze thawing supematant of bladder tumor cells group(P <0.001). Conclusion Sensitized DC injecting subcutaneously can reduce the stages of F344 rats' bladder tumor, Unsensitized DC injecting subcutaneously has not effect in the treatment of bladder tumor;, while the effect of freeze thawing supematant of tumor cells injecting subcutaneously is not well. The mechanism of sensitized DC in the treatment of blader tumor is that DC plays an immunol killing role by presenting antigen, stimulating CTL.