1.HU value of chest CT vertebral body in the opportunistic screening of type 2 diabetes mellitus osteoporosis
Liping WANG ; Tianxing LIAN ; Yongrong HU ; Hongsheng YANG ; Zhimou ZENG ; Hao LIU ; Bo QU
Chinese Journal of Tissue Engineering Research 2024;28(6):950-954
BACKGROUND:Some studies have shown that the hounsfield units(HU)value based on lumbar CT can be used to screen osteoporosis.At present,the number of patients with pulmonary infection has increased;the number of patients with pulmonary infection and type 2 diabetes is also increasing,which increases the utilization rate of chest CT. OBJECTIVE:To investigate the role of lumbar 1 vertebral body HU value based on chest CT in the screening of type 2 diabetes mellitus osteoporosis. METHODS:The clinical data of 244 patients with type 2 diabetes mellitus treated in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022 were analyzed retrospectively.The bone mineral density was obtained by dual-energy X-ray absorptiometry.According to WHO's diagnostic criteria for osteoporosis,the subjects were divided into the non-osteoporosis group(n=120)and the osteoporosis group(n=124).The general condition,T value and HU value of lumbar 1 vertebra in chest CT were compared,and the relationship between the HU value and T value of each position was analyzed and the accuracy of type 2 diabetes mellitus osteoporosis was evaluated. RESULTS AND CONCLUSION:(1)There was no significant difference in sex,age,body mass index,glycosylated hemoglobin,mean blood glucose,calcium(Ca),phosphorus(P),time of type 2 diabetes mellitus,history of hypertension and history of hyperlipidemia between the two groups(P>0.05).(2)The HU value was positively correlated with the lowest T value of the hip(r=0.619,P<0.01);the HU value was positively correlated with the hip T value(r=0.584,P<0.01),and the HU value was positively correlated with the femoral neck T value(r=0.641,P<0.01).When the HU value was 98,the prediction of type 2 diabetes mellitus osteoporosis had good accuracy,and the sensitivity was 70.8%.(3)It is concluded that the HU value of the lumbar 1 vertebra based on chest CT examination is of good value for osteoporosis screening in patients with type 2 diabetes mellitus,and may be an opportunistic and cost-free supplementary screening method for type 2 diabetes mellitus osteoporosis.
2.Construction of nucleus pulposus spherical cell clusters and their functional repair in rat intervertebral disc degeneration model
Yang LIU ; Sifan AI ; Yiming DOU ; Ye TIAN ; Bo GAO ; Xun SUN ; Zhimou YANG ; Xinlong MA ; Qiang YANG
Chinese Journal of Orthopaedics 2024;44(23):1549-1558
Objective:To explore the repair effect of nucleus pulposus spherical cell clusters in the process of intervertebral disc degeneration and its potential therapeutic application.Methods:The degradation and rheological properties of SupraGel hydrogel were characterized, and the biocompatibility of spherical nucleus pulposus cell clusters in SupraGel hydrogel was tested by live-dead cytological staining. A caudal disc puncture degeneration model was established in 20 SD rats, and the rats were divided into groups and intervention measures: puncture of degenerated segment without intervention (positive control group), puncture of degenerated segment injection of SupraGel hydrogel (hydrogel group), puncture of degenerated segment injection of spherical cell clusters (cell cluster group), puncture of degenerated segment injection of SupraGel hydrogel loaded with spherical cell clusters (hydrogel + cell cluster group) and healthy segment (negative control group). X-rays and MRI examinations were performed at the 4th and 8th weeks after intervention, and the disc degeneration was evaluated according to the disc height index and Pfirrmann grading. HE staining, safranin O-fast green staining and COL-2 immunohistochemical staining were used to evaluate the changes in the disc structure and extracellular matrix.Results:The degradation residual rate of SupraGel hydrogel was 73.7% after 10 h, which showed excellent shear thinning and self-recovery properties. Nucleus pulposus cells could spontaneously aggregate in SupraGel hydrogel to form stable spherical cell clusters, which remained active on the 7th day. In the in vivo experiment, the intervertebral height index of the hydrogel + cell cluster group was 88.12%±4.55% and 74.13%±4.09% at 4 and 8 weeks after intervention, which were higher than those of the positive control group and hydrogel group, and lower than those of the negative control group, with statistically significant differences ( P<0.05); the Pfirrmann grades were 2.40±0.55 and 2.60±0.89, which were lower than those of the positive control group and hydrogel group at 4 weeks, and lower than those of the positive control group, hydrogel group and cell cluster group at 8 weeks, and higher than those of the negative control group, with statistically significant differences ( P<0.05); the morphological scores were 6.60±0.55 and 9.40±1.14, which were lower than those of the positive control group, hydrogel group and cell cluster group at 4 weeks, at the 8th week, the levels of collagen type II were lower than those of the positive control group, hydrogel group and cell cluster group, but higher than those of the negative control group, and the difference was statistically significant ( P<0.05). The optical density of type II collagen was 0.12±0.01 and 0.10±0.01, respectively, which were higher than those of the positive control group, hydrogel group and cell cluster group at the 4th week, and higher than those of the positive control group and hydrogel group at the 8th week, and the difference was statistically significant ( P<0.05). Conclusion:Nucleus pulposus spherical cell clusters can be successfully constructed and have been shown to have the effect of delaying degeneration in the rat intervertebral disc degeneration model.
3.Construction of nucleus pulposus spherical cell clusters and their functional repair in rat intervertebral disc degeneration model
Yang LIU ; Sifan AI ; Yiming DOU ; Ye TIAN ; Bo GAO ; Xun SUN ; Zhimou YANG ; Xinlong MA ; Qiang YANG
Chinese Journal of Orthopaedics 2024;44(23):1549-1558
Objective:To explore the repair effect of nucleus pulposus spherical cell clusters in the process of intervertebral disc degeneration and its potential therapeutic application.Methods:The degradation and rheological properties of SupraGel hydrogel were characterized, and the biocompatibility of spherical nucleus pulposus cell clusters in SupraGel hydrogel was tested by live-dead cytological staining. A caudal disc puncture degeneration model was established in 20 SD rats, and the rats were divided into groups and intervention measures: puncture of degenerated segment without intervention (positive control group), puncture of degenerated segment injection of SupraGel hydrogel (hydrogel group), puncture of degenerated segment injection of spherical cell clusters (cell cluster group), puncture of degenerated segment injection of SupraGel hydrogel loaded with spherical cell clusters (hydrogel + cell cluster group) and healthy segment (negative control group). X-rays and MRI examinations were performed at the 4th and 8th weeks after intervention, and the disc degeneration was evaluated according to the disc height index and Pfirrmann grading. HE staining, safranin O-fast green staining and COL-2 immunohistochemical staining were used to evaluate the changes in the disc structure and extracellular matrix.Results:The degradation residual rate of SupraGel hydrogel was 73.7% after 10 h, which showed excellent shear thinning and self-recovery properties. Nucleus pulposus cells could spontaneously aggregate in SupraGel hydrogel to form stable spherical cell clusters, which remained active on the 7th day. In the in vivo experiment, the intervertebral height index of the hydrogel + cell cluster group was 88.12%±4.55% and 74.13%±4.09% at 4 and 8 weeks after intervention, which were higher than those of the positive control group and hydrogel group, and lower than those of the negative control group, with statistically significant differences ( P<0.05); the Pfirrmann grades were 2.40±0.55 and 2.60±0.89, which were lower than those of the positive control group and hydrogel group at 4 weeks, and lower than those of the positive control group, hydrogel group and cell cluster group at 8 weeks, and higher than those of the negative control group, with statistically significant differences ( P<0.05); the morphological scores were 6.60±0.55 and 9.40±1.14, which were lower than those of the positive control group, hydrogel group and cell cluster group at 4 weeks, at the 8th week, the levels of collagen type II were lower than those of the positive control group, hydrogel group and cell cluster group, but higher than those of the negative control group, and the difference was statistically significant ( P<0.05). The optical density of type II collagen was 0.12±0.01 and 0.10±0.01, respectively, which were higher than those of the positive control group, hydrogel group and cell cluster group at the 4th week, and higher than those of the positive control group and hydrogel group at the 8th week, and the difference was statistically significant ( P<0.05). Conclusion:Nucleus pulposus spherical cell clusters can be successfully constructed and have been shown to have the effect of delaying degeneration in the rat intervertebral disc degeneration model.
4.Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death.
Debin ZHENG ; Jingfei LIU ; Limin XIE ; Yuhan WANG ; Yinghao DING ; Rong PENG ; Min CUI ; Ling WANG ; Yongjie ZHANG ; Chunqiu ZHANG ; Zhimou YANG
Acta Pharmaceutica Sinica B 2022;12(6):2740-2750
Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

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