1.Engineered stem cell bionic periosteum coordinates immune inflammation and vascularization to promote bone regeneration
Huiwen SUN ; Qiangqiang GUO ; Wei WANG ; Jie WU ; Kun XI ; Yong GU
Chinese Journal of Tissue Engineering Research 2026;30(1):21-33
BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.
2.Differences in scapular kinematics between healthy individuals and rotator cuff tear patients based on biplane X-ray
Zicheng GUO ; Jingyuan MENG ; Jiechao ZHANG ; Li DING ; Xiaoye TANG ; Lichao TIAN ; Yilin WANG ; Yong HE
Chinese Journal of Tissue Engineering Research 2026;30(3):652-660
BACKGROUND:Due to the complex movement of the scapula,which is a six-degree-of-freedom activity in three-dimensional space,it is difficult to measure it accurately using traditional methods.The image and model matching technology based on dual-plane X-ray is a three-dimensional measurement method that has gradually developed and matured in recent years.Two high-speed cameras are used to project and shoot from orthogonal directions.Compared with a single perspective,this method has advantages in observation range and reduction of out-of-plane errors,and is suitable for the study of scapula kinematics.OBJECTIVE:X-ray biplane and image-model registration technology were used to explore the differences in scapular kinematics between normal individuals and patients with rotator cuff tears,providing a basis for the treatment and rehabilitation of rotator cuff tear patients.METHODS:From April 2023 to January 2024,10 patients with normal shoulders and 10 patients with rotator cuff tears who met the inclusion criteria were enrolled from Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The subjects underwent a shoulder CT scan to create a 3D model and a local scapular coordinate system.X-ray biplane images were taken during shoulder abduction with two C-arm machines.The 2D and 3D images were registered to compare scapular kinematic differences between the two groups at 0°,15°,30°,45°,60°,75°,and 90° of abduction,including scapular rotation angle and displacement distance.RESULTS AND CONCLUSION:(1)During shoulder abduction,the scapula of both groups showed upward rotation,but the upward rotation of the rotator cuff tear group was greater than that of the control group,and the difference was significant when the abduction was 30°-90°(P<0.01).At the same time,the scapula internal rotation of both groups gradually increased,but the rotator cuff tear group was significantly greater than the control group when the abduction was 45°-90°(P<0.01).In addition,the anteroposterior tilt of the scapula of the two groups was significantly different when the abduction was 15°-90°(P<0.01).The scapula posterior tilt of the control group gradually increased during abduction,while the scapula of the rotator cuff tear group tilted forward except for a slight posterior tilt at 15°-30° abduction.(2)In terms of displacement,the upward displacement of the rotator cuff tear group was less than that of the control group during abduction,and the difference was significant at 15°-90°(P<0.05),but there was no significant difference in lateral and anterior-posterior displacement between the two groups(P>0.05).(3)Rotator cuff tear can cause scapular dyskinesis,characterized by increased upward rotation,internal rotation,and abnormal forward tilt during shoulder abduction.Identifying and addressing scapular dyskinesis is crucial for treating rotator cuff tear.
3.Research on the construction and application of blood standard system in China
Jin GUO ; Hongjie WANG ; Xin SHI ; Yong WANG
Chinese Journal of Blood Transfusion 2026;39(4):564-570
Blood standardization is a crucial means of promoting the healthy and sustainable development of China's blood industry. The construction of a blood standard system serves as the foundational work for blood standardization. To facilitate the continuous improvement of blood standardization efforts, this paper begins by describing the current status and analyzing the issues within China's blood standard system. Through systematic research, it proposes a framework for constructing a blood standard system and offers revision recommendations for its enhancement. Based on the first five editions of the blood standard system developed by Sub-Committee of Blood Standards of National Committee of Health Standards, this study further refines the revision and detailed construction of the standards framework—the primary task in establishing the blood standard system. It provides specific guidance for both the construction and application of the blood standard system. This work serves as a reference and basis for the reasonable and standardized formulation and revision of blood standards, as well as for the management and implementation of blood standardization efforts.
4.Engineered stem cell bionic periosteum coordinates immune inflammation and vascularization to promote bone regeneration
Huiwen SUN ; Qiangqiang GUO ; Wei WANG ; Jie WU ; Kun XI ; Yong GU
Chinese Journal of Tissue Engineering Research 2026;30(1):21-33
BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.
5.Differences in scapular kinematics between healthy individuals and rotator cuff tear patients based on biplane X-ray
Zicheng GUO ; Jingyuan MENG ; Jiechao ZHANG ; Li DING ; Xiaoye TANG ; Lichao TIAN ; Yilin WANG ; Yong HE
Chinese Journal of Tissue Engineering Research 2026;30(3):652-660
BACKGROUND:Due to the complex movement of the scapula,which is a six-degree-of-freedom activity in three-dimensional space,it is difficult to measure it accurately using traditional methods.The image and model matching technology based on dual-plane X-ray is a three-dimensional measurement method that has gradually developed and matured in recent years.Two high-speed cameras are used to project and shoot from orthogonal directions.Compared with a single perspective,this method has advantages in observation range and reduction of out-of-plane errors,and is suitable for the study of scapula kinematics.OBJECTIVE:X-ray biplane and image-model registration technology were used to explore the differences in scapular kinematics between normal individuals and patients with rotator cuff tears,providing a basis for the treatment and rehabilitation of rotator cuff tear patients.METHODS:From April 2023 to January 2024,10 patients with normal shoulders and 10 patients with rotator cuff tears who met the inclusion criteria were enrolled from Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The subjects underwent a shoulder CT scan to create a 3D model and a local scapular coordinate system.X-ray biplane images were taken during shoulder abduction with two C-arm machines.The 2D and 3D images were registered to compare scapular kinematic differences between the two groups at 0°,15°,30°,45°,60°,75°,and 90° of abduction,including scapular rotation angle and displacement distance.RESULTS AND CONCLUSION:(1)During shoulder abduction,the scapula of both groups showed upward rotation,but the upward rotation of the rotator cuff tear group was greater than that of the control group,and the difference was significant when the abduction was 30°-90°(P<0.01).At the same time,the scapula internal rotation of both groups gradually increased,but the rotator cuff tear group was significantly greater than the control group when the abduction was 45°-90°(P<0.01).In addition,the anteroposterior tilt of the scapula of the two groups was significantly different when the abduction was 15°-90°(P<0.01).The scapula posterior tilt of the control group gradually increased during abduction,while the scapula of the rotator cuff tear group tilted forward except for a slight posterior tilt at 15°-30° abduction.(2)In terms of displacement,the upward displacement of the rotator cuff tear group was less than that of the control group during abduction,and the difference was significant at 15°-90°(P<0.05),but there was no significant difference in lateral and anterior-posterior displacement between the two groups(P>0.05).(3)Rotator cuff tear can cause scapular dyskinesis,characterized by increased upward rotation,internal rotation,and abnormal forward tilt during shoulder abduction.Identifying and addressing scapular dyskinesis is crucial for treating rotator cuff tear.
6.Clinical efficacy of repetitive transcranial magnetic stimulation at different frequencies in the treatment of multiple system atrophy
Journal of Apoplexy and Nervous Diseases 2026;43(4):343-348
Objective To identify the effective therapeutic targets of multiple system atrophy-parkinsonian type (MSA-P) based on clinical and electrophysiological assessment indices, and to investigate the clinical efficacy of low-frequency versus high-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the primary motor cortex (M1 region) of the brain in patients with MSA-P. Methods A total of 40 patients with MSA-P who were diagnosed and treated in Jilin People’s Hospital from January 2023 to December 2024 were enrolled, and according to the frequency of rTMS, they were divided into low-frequency group with 20 patients and high-frequency group with 20 patients. The patients in the low-frequency group received 1 Hz rTMS over the M1 region, while those in the high-frequency group received 5 Hz rTMS over the M1 region, and clinical and electrophysiological assessments were performed for both groups at 1 week, 2 weeks, 4 weeks, and 3 months after intervention. Results After low-frequency or high-frequency rTMS was applied to the M1 region of MSA-P patients, there were no significant improvements in clinical and electrophysiological assessment indices in the low-frequency group, while the high-frequency group had significant improvements in clinical and electrophysiological assessment indices. Conclusion The primary motor cortex (M1 region) of the brain is an effective therapeutic target for MSA-P. Excitatory stimulation of the M1 region significantly improves the clinical and electrophysiological assessment indices of MSA-P, while inhibitory stimulation of the M1 region fails to achieve such improvements. This study shows that rTMS is an effective therapeutic modality for MSA-P and thus holds promise for clinical application. High-frequency rTMS over the M1 region can improve the symptoms of MSA-P and correct abnormal rhythmic activity within the cortex and related subcortical brain regions, thereby achieving a sustained therapeutic effect.
7.Treatment Modalities and Long-Term Outcomes in Unruptured Vertebrobasilar Fusiform Aneurysms: A Nationwide Observational Cohort Study
Linggen DONG ; Dachao WEI ; Xiheng CHEN ; Mingtao LI ; Yang ZHAO ; Yong SUN ; Qingbin NIE ; Jun FENG ; Guomin XIAO ; Jinghua ZHOU ; Shengli HU ; Lifei FENG ; Lifeng QI ; Hongen LIU ; Geng GUO ; Yufang LI ; Renfu TIAN ; Jianghua YU ; Dianshi JIN ; Liang HAO ; Tian TIAN ; Shizhong ZHANG ; Yang WANG ; Liping LIU ; Ming LV
Journal of Stroke 2026;28(2):250-262
Background:
and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis.
Methods:
This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed.
Results:
Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs.
Conclusions
Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.
8.Comparison of the prognostic predictive efficacy of three frailty screening scales in elderly patients in the emergency department
Huizhen LIU ; Guodong WANG ; Yong SHANG ; Na SHANG ; Junyu LI ; Na WANG ; Xiaomeng LIU ; Shubin GUO ; Suxia MA
Chinese Journal of Emergency Medicine 2025;34(1):55-61
Objective:To investigate the association between frailty and prognosis of elderly patients in the emergency department, and to validate frailty screening tools suitable for the emergency department.Methods:This was a prospective cohort study. Clinical data of elderly patients over 60 years old treated in the emergency department of Beijing Bo'Ai Hospital from January to December 2021 were collected. The Frailty Screening Questionnaire (FSQ), FRAIL Scale (FRAIL) and Clinical Frailty Scale (CFS) were used to score patients, and patients were divided into frail or non-frail group according to the criteria of the above three scales. Twelve-month all-cause mortality was the primary endpoint, dependence and re-admission to the emergency department within 12 months were secondary outcomes. Receiver operating characteristic curves were used to evaluate the ability of the FSQ, FRAIL and CFS scores to predict the primary and secondary endpoints, and the areas under the curve (AUC) were calculated and compared. Survival analysis was performed using Cox hazard proportional regression model, and relative risk was expressed as hazard ratio ( HR) and 95% CI. Results:A total of 406 patients were included in the study. The AUCs (95% CI) of FSQ, FRAIL and CFS scores for predicting 12-month all-cause mortality were 0.879 (0.844-0.909), 0.838 (0.798-0.872), 0.906 (0.873-0.933), respectively (all P<0.001). The AUCs of 3 scores for predicting secondary endpoints ranged from 0.820 to 0.889 (all P<0.001). Pairwise comparisons of the AUCs showed that the CFS was superior to one or both of the other frailty screening scales in predicting 12-month all-cause mortality and dependence except for re-admission to emergency room within 12 months after discharge (all P<0.05). Cox regression analysis revealed that, after adjusting for sex, age, body mass index and comorbidities, frailty as defined by the FSQ, FRAIL, and CFS scales was independently associated with 12-month all-cause mortality, with the HRadj of 3.267 (95% CI: 2.406-4.435), 2.465 (95% CI: 1.819-3.341), 3.523 (95% CI: 2.648-4.687), respectively (all P<0.001). Conclusions:FSQ, FRAIL and CFS scores can predict adverse outcomes, the CFS is a practical frailty screening tool in the emergency department, and frailty screening can improve the risk stratification of older patients.
9.Effect of neutrophil elastase inhibitor on acute respiratory distress syndrome in children
Hua ZHANG ; Weikai WANG ; Zhangyan GUO ; Yanqiang DU ; Yong ZHOU ; Yi WANG
International Journal of Pediatrics 2025;52(1):55-60
Objective:To investigate the efficacy of neutrophil elastase inhibitor in children with acute respiratory distress syndrome(ARDS).Methods:A total of 168 children with moderate to severe ARDS who were hospitalized in the Department of Pediatric Intensive Care Unit,the Affiliated Children′s Hospital of Xi′an Jiaotong University and Children's Emergency Center of Gansu Provincial Central Hospital from January 2022 to December 2023 were selected. Eighty-seven children receiving neutrophil elastase inhibitors were treated as the treatment group and 81 children receiving conventional treatment as the control group. The dynamic changes of general data,clinical indicators and ventilator parameters at 24 h,48 h and 72 h were compared between the two groups. Mortality at 28 days was the primary endpoint. Kaplan-Meier curve and Log-Rank test were used to evaluate cumulative survival.Results:There was no significant difference in general information and clinical characteristics between the two groups.Compared with the control group,arterial partial pressure of oxygen(PaO 2)/fraction of inspired oxygen(FiO 2)in the treatment group increased significantly at 48 h[(160.28±5.90)mmHg(1 mmHg=0.133 kPa)vs(141.04±4.01)mmHg, P<0.05]and 72 h[(227.58±6.85)mmHg vs(180.86±4.08)mmHg, P<0.05],and the differences were statistically significant.The platform pressure in the treatment group were lower than that of the control group at 24 h[(28.18±3.95)cmH 2O(1cmH 2O=0.098 kPa)vs(30.15±7.75)cmH 2O, P<0.05],48 h[(25.56±4.06)cmH 2O vs(29.07±5.01)cmH 2O, P<0.05],72 h[(24.95±2.82)cmH 2O vs(27.12±6.51)cmH 2O, P<0.05],and the differences were statistically significant. IL-8 in the treatment group were lower than that of the control group at 48 h[(78.26±14.05)ng/L vs(86.02±15.01)ng/L, P<0.05]and 72 h[(58.38±15.56)ng/L vs(68.68±18.05)ng/L, P<0.05],and the differences were statistically significant.The survival curve showed that the cumulative survival rate of the treatment group was higher than that of the control group,the difference between the two groups was statistically significant( χ2=4.549, P=0.033). Conclusion:Neutrophil elastase inhibitors can reduce the lung injury of ARDS patients by inhibiting the inflammatory response induced by neutrophils,and ultimately improve the prognosis of the disease.
10.Research status and progress in animal models of senile osteoporosis
Tonghai ZHANG ; Lining WANG ; Yongkang HU ; Tianci MA ; Anyang HAN ; Yong MA ; Yang GUO
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):440-448
Senile osteoporosis is a growing public health challenge with significant impacts on the daily life of the elderly population as a result of its hidden nature,high prevalence,and high risk of disability.Suitable animal models that simulate senile osteoporosis are crucial for understanding its pathological mechanism and to facilitate the development of anti-osteoporosis drugs and identify new therapeutic targets.This review considers the most commonly used method for creating animal models of senile osteoporosis,analyzes their advantages and limitations,and discusses research progress in animal models in terms of evaluation indicators,to provide references for research using animal models of senile osteoporosis.

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