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Imaging Evaluation And Basic Research On Treatment Of OVCF

Posted on:2023-11-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z R ZhengFull Text:PDF
GTID:1524306773461924Subject:Surgery (bone)
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Background: Osteoporotic vertebral compression fracture(OVCF)is the most common complication of osteoporosis.It affects the work and life of more than 700000 Americans every year.Four in 10 women over the age of 50 have experienced hip or spinal fractures in their lifetime,and the risk of fracture increases with age.Although a large number of studies and reports have proposed the prevention,diagnosis and treatment strategies of osteoporotic fractures,there are still few effective ways of OVCF prevention,diagnosis and treatment.Therefore,it is particularly important to find out the risk and treatment mechanism of OVCF and understand the specific efficacy of anti osteoporosis drugs designed for OVCF.Objective: By using mobile instant messaging software to improve the follow-up after vertebral augmentation,by using the follow-up imaging database to evaluate the risk of OVCF,and by using the clues found from the risk to design and verify peptide nanoparticles for OVCF basic treatment.Methods: 1)The data and follow-up records of 559 patients who underwent OVCF vertebroplasty in our institution from December 2015 to May 1,2021 were collected.368 patients were followed up by instant messaging App(JSTX.App)and 191 patients were followed up by telephone.All data were analyzed by SUS questionnaire for follow-up effectiveness of App.By comparing the input and query speed with the traditional instant messaging software(XSLBLJ.App),and by verifying the measurement speed and consistency in imaging,the imaging availability of JSTX.App were edvaluated.2)Through JSTX.App follow-up imaging database,imaging parameters of spinal flexion in OVCF were screened,154 cases of menopausal OVCF and 310 cases of menopausal non OVCF were included.The correlation between incidence rate of OVCF and thoracolumbar hyperflexion Cobb’s angle(TLHCobb’s)was analyzed.The other,102 cases of menopausal thoracolumbar OVCF and 210 cases of menopausal non OVCF were included.The correlation between the incidence rate of thoracolumbar OVCF and the range of motion of thoracolumbar flexion(difference of Cobb’s angle of thoracolumbar segment motion flexion,DCTL)was analyzed.According to the comprehensive analysis,the increased risk of OVCF is caused by the increase of vertebral Cobb’s angle.3)However,the decrease of vertebral BMD caused by osteoclast hyperactivity of chronic inflammation in osteoporosis and acute inflammation in OVCF is the key factor for the increase of Cobb’s angle.A anti-osteoporotic peptide targeting bone inflammatory tissue and inhibiting osteoclast activity was designed.RAW264.7 and BMMs were tested to verify the cytological function of the peptide functional region by inhibiting osteoclast formation ability and cytotoxicity with different short peptides;inhibiting osteoclast activity with different concentrations;inhibiting osteoclast formation activity at different stages,osteoclast apoptosis;inhibiting the expression of characteristic m RNA of osteoclasts.By the distribution experiment in rats,OVCF site targeting of the peptide was verified.Andrographolide granules coated with the peptides were used to conduct animal experiments in mice to explore the effectiveness of anti-osteoporosis.Results: 1)By JSTX.App,the most reasons for OVCF postoperative consultation in the follow-up of App group was effectively identified and patients’ problems was solved timely,that making it easier for patients to maintain long-term contact with medical institutions.JSTX.App is faster and more specialized than XSLBLJ.App in input and query.Compared with traditional desktop computer software,JSTX.App imaging measurement is faster and consistent.2)A total of 350 cases with OVCF were collected.The incidence of vertebral compression fracture was significantly correlated with TLHCobb’s.TLHCobb’s exceeded 20.05°,the corresponding OR=4.83(3.24-7.20),the sensitivity 86.1%,the specificity 86.1%,and AUC=0.754(0.708-0.800)were shown.The incidence of thoracolumbar OVCF was significantly correlated with DCTL.DCTL≤8.7°,OR=9.95(5.31-18.64),sensitivity 78.4%,specificity 74.3%,OR=9.95 and AUC=0.783(0.61-0.953)were shown.3)SDCECSRR-GDLG,GG-SDCECSRR-GDLG and C18-GG-SDCECSRR-GDLG(a fragment of C18-GG-SDCECSRR-GDLGLAGQ-LRELHLNNN(D peptide)digested by MMP9),three peptides still retained the activity of inhibiting osteoclast formation.These peptides inhibited osteoclast formation more strongly in the early stage than in the late stage.They had no significant cytotoxicity in the concentration of 400ug/ml,did not cause osteoclast significant apoptosis,and significantly inhibited the expression of characteristic genes such as TRAP,CTSK and MMP9 in osteoclasts.It was preliminarily found that the D peptide could target OVCF sites one week after fracture and D-coated andrographolide granules had the effectiveness of anti-osteoporosis in OVX mice.Conclusion: 1)Compared with the traditional telephone consultation service,JSTX.App consultation service is more timely,effective,convenient,intuitive and comprehensive.It may have a strong effect in finding and dealing with postoperative problems in time,controlling the occurrence of adverse events and establishing a long-term and stable doctor-patient relationship.Compared with traditional computer software,JSTX.App have the function of imaging data collection.It’s imaging measurement is available and convenient,which can further improve the efficiency of medical professionals in using the OVCF imaging database.2)There was a relationship between the incidence of OVCF and TLHCobb’s in menopausal women,and a TLHCobb’s>20.05° can be an indicator of vertebral fracture.Low DCTL may be a risk representation of thoracolumbar OVCF in menopausal women,and a DCTL≤8.7° can be a threshold value of thoracolumbar OVCF.3)SDCECSRR-GDLG,GG-SDCECSRR-GDLG and C18-GG-SDCECSRR-GDLG,three peptides can effectively inhibit osteoclast formation from RAW264.7 and BMMs,especially in the early stage of osteoclast formation.These peptides had no significant cytotoxicity and did not cause significant apoptosis.D peptide could target OVCF sites in early stage of fracture.Andrographolide coated with the peptide had the possibility of anti-osteoporosis in OVX mice.
Keywords/Search Tags:OVCF, spinal flexion position, nanopeptide drug delivery
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