1.Parecoxib sodium alleviates pain in rats with femoral fractures by modulating TLR4/p38MAPK pathway
Hua WANG ; Huili SHEN ; Liyun DONG ; Shuqing ZHEN ; Guangping ZHAO ; Yongxue CHEN ; Xinbo WANG ; Jianhua LI
Immunological Journal 2025;41(4):237-242
Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P<0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P<0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.
2.Parecoxib sodium alleviates pain in rats with femoral fractures by modulating TLR4/p38MAPK pathway
Hua WANG ; Huili SHEN ; Liyun DONG ; Shuqing ZHEN ; Guangping ZHAO ; Yongxue CHEN ; Xinbo WANG ; Jianhua LI
Immunological Journal 2025;41(4):237-242
Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P<0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P<0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.
3.Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 pathway
Xinyan LIU ; Liyun DONG ; Peipei ZHOU ; Yongxue CHEN ; Xinbo WANG ; Yan SUN
Journal of Clinical Medicine in Practice 2024;28(15):19-25
Objective To investigate the effects of esketamine on hypoxic-ischemic myocardial injury in neonatal rats based on glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 (GSK-3β/NLRP3) pathway. Methods Thirty neonatal rats were randomly divided into sham operation group, model group and esketamine group, with 10 rats in each group. The rats in the sham operation group underwent a median incision in the neck to expose the bilateral common carotid arteries; the rats in the model group and the esketamine group underwent ligation of the common carotid arteries combined with a hypoxic environment to establish a model ofischemia and hypoxia; the rats in the esketamine group were given esketamine intervention (50 mg/kg). Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β levels, myocardial injury, myocardial cell apoptosis and apoptosis protein caspase 1/3/9 levels, neutrophil infiltration in myocardial tissue, and changes in GSK-3β and NLRP3 protein levels in myocardial tissue were detected in each group. Results Compared with the sham operation group, the LVEF and LVFS were significantly decreased and the LVEDD and LVESD were significantly increased in the model group, while the LVEF and LVFS were significantly higher and the LVEDD and LVESD were significantly lower in the esketamine group than in the model group (
4.Prognostic value of thrombin generation assay and coagulation factor testing in postoperative deep venous thrombosis of lower extremities in elderly patients with traumatic fracture
Xinbo ZHANG ; Haishan WAN ; Dong CHEN ; Ye QU
Journal of Clinical Surgery 2023;31(11):1100-1103
Objective To analyze the prognostic value of thrombin generation assay(TGA)and coagulation factor testing in postoperative deep venous thrombosis(DVT)of lower extremities in elderly patients with traumatic fracture.Methods A retrospective case-control study was conducted to collect traumatic patients older than 60 years old who underwent surgery in our department from March 2019 to March 2022.The number of patients was 104.According to the ultrasonic examination of DVT 5 days after operation,the patients were divided into DVT group and non-DVT group.The differences of general demographic data,previous chronic diseases,time from trauma to operation,related indexes of TGA and TF coagulation factors(F)between the two groups were analyzed.The indexes with statistical significance were analyzed by receiver operating curve(ROC);the indexes with statistically significant differences were analyzed by Logistic regression and the prediction probability was calculated by ROC curve analysis.Results The incidence of postoperative DVT was 21.12%.Compared with the non-DVT group,the time from trauma to operation was longer in the DVT group,and the peak value under 5 pmol/L TF activation was lower(258.13±40.88 vs 209.58±30.09).F V,F Ⅷ and Fib were higher(141.25(125.38,158.18)vs 176.12(150.65,186.34),145.49(133.36,147.48)vs 165.96(153.07,180.65),3.25± 0.55 vs 3.92±0.72,respectively).The differences were statistically significant(all P<0.01).ROC curve analysis showed that the time from trauma to operation,the peak value of 5 pmol/L TF activation,F V,FⅧ and Fib combined had more predictive value for postoperative DVT,the AUC was 0.91(P<0.01),the sensitivity was 0.82 and the specificity 0.92.Conclusion The time from trauma to operation,the peak value of TGA under the condition of 5 pmol/L TF activation,F V,F Ⅷ and Fib have excellent prognostic value for the postoperative DVT of lower extremities in elderly patients with traumatic fracture,and the combined detection is more significative.
5.Regulation of swimming motility by H-NS in Vibrio parahaemolyticus
Jie WANG ; Lei LIN ; Fengjun SUN ; Xinbo DONG ; Shuning HOU ; Dongsheng ZHOU ; Zhe YIN ; Yiquan ZHANG
Military Medical Sciences 2015;(9):694-697
Objective To investigate the regulation of swimming motility by H-NS in Vibrio parahaemolyticus(VP). Methods VP was inoculated into the semi-solid swimming agar plate containing 1% Oxoid tryptone, 2% NaCl, 0.5%Difco Noble Agar, and 0.1% arabinose followed by incubation at 37℃ for 4.5 h before the diameters of bacterial lawns were measured.Total RNAs were extracted from the wild-type (WT) strains and the hns null mutant (Δhns), and the quantitative real-time( RT)-PCR( qRT-PCR) was carried out to calculate the transcriptional variation of flaA between WT andΔhns strains.The entire promoter DNA region of flaA was amplified and cloned into the lacZ fusion vector pHRP309 containing a promoterless lacZ gene. The recombinant lacZ reporter plasmid was transformed into WT and Δhns, respectively, to measure the β-galactosidase activities in cellular extracts using the β-galactosidase enzyme assay system. Results and Conclusion The phenotype results showed that swimming motility of VP was enhanced by H-NS.The qRT-PCR and LacZ fusion results indicated that the transcription of flaA was positively regulated by H-NS.Collectively, H-NS promotes the swimming motility of VP, at least partly, by activating the transcription of flaA.
6.Effect of salinity and temperature on motility of Vibrio parahaemolyticus
Xinbo DONG ; Yiquan ZHANG ; Ruifu YANG ; Chuanxiao XIE ; Dongsheng ZHOU
Military Medical Sciences 2014;(12):962-964
Objective To investigate the effect of salinity and temperature on motility of Vibrio parahaemolyticus. Methods V.parahaemolyticus was inoculated on swarming or swimming agar plates containing different amounts of salinity (0.5%, 1.0%, 2.0%, and 4.0% NaCl, respectively), followed by incubation at 26 or 37℃, before the diameters of bacterial lawns were measured .Results and Conclusion The swarming motility was not affected by salinity , while the swimming motility was positively correlated with salinity .Maximum swimming occurred in 2.0% NaCl, and displayed a slight decline in salinity of 4.0%.Both swimming and swarming were affected by temperature , and the motility was signifi-cantly enhanced in 37℃vs 26℃.These results indicate that both salinity and temperature can modulate the motility of V. parahaemolyticus.
7.Study on the preparation and application of individual artificial bone with carbon/carbon composites.
Xinye NI ; Nong QIAN ; Dong ZHOU ; Yunliang MIAO ; Xinbo XIONG ; Tao LIN ; Da CHEN ; Gongyin ZHAO ; Ping ZHONG
Journal of Biomedical Engineering 2013;30(6):1265-1271
The present paper is aimed to study the preparation and application of individual artificial bone of carbon/carbon composites. Using computer tomography images (CT), we acquired a three-dimensional image. Firstly, we described bone contour line outlined with manual and automatic method by the binary volume data. Secondly, we created 3D object surface information by marching cubes. Finally, we converted this information to non-uniform rational B-spine (NURBS) by using geomagic software. Individual artificial bone with carbon/carbon composite was prepared through the CNC Machining Center. We replaced the humeral head of the tested rabbit, and then observed the effects of implantation in neuroimaging and pathological section. Using this method, we found that the bone shape processed and bone shape replaced was consistent. After implantation, the implant and the surrounding bone tissue bound closely, and bone tissue grew well on the surface of the implant. It has laid a sound foundation of the preparation using this method for individual artificial bone of carbon/carbon composite material.
Animals
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Bone Substitutes
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chemistry
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Carbon
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chemistry
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Imaging, Three-Dimensional
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Rabbits
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Software
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Tomography, X-Ray Computed
8.Protective effects of dexamethasone against ototoxicity in guinea pigs
Xinbo ZHU ; Xiaodong JIN ; Miaowu DONG ; Dan LIN
Chinese Journal of Clinical Pharmacology and Therapeutics 2002;0(06):-
AIM: To study the protective effects of dexamethasone agains t ototoxicity of aminoglycoside antibiotics in guinea pigs. METHODS: Guinea pigs were divided into five groups. Group One: gentamycin, im; Group Two: amikacin, im; Group Three: gentamycin+ dexamethasone, im; Group Four: amika cin+ dexamethasone,im; Group Five: NS, im, all for two weeks. After three weeks, all animals were examined including tympanic mucous membrane reaction, nystagmu s depression rates and cochleae morphology. RESULTS: In Group Th ree and Four, the changes of morphology were slighter than those in Group One an d Two. CONCLUSION: Dexamethasone can weaken ototoxicity of amino glycoside antibiotics.


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