Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Efficacy of transforaminal endoscopic nerve root decompression in the treatment of degenerative lumbar spinal stenosis / 北京大学学报(医学版)

Objective:To evaluate the feasibility of transforaminal endoscopic nerve root decompression for degenerative lumbar spinal stenosis (DLSS).Methods: From July 2011 to April 2016,96 cases of single segment DLSS were involved.All the patients had unilateral lower extremity neurological symptoms,signs,neurogenic intermittent claudication of less than 500 m.Imaging examinations (CT or MRI) or diagnostic nerve root block confirmed single segment degeneration.The mean age was (71.6±5.4) years,male: 55 cases,female: 41 cases.Their intraoperative blood loss,operation time,complications,ambulation time and discharge time were recorded.Leg pain VAS,ODI were used to evaluate the pain and lumbar function of the patients.The clinical efficacy was evaluated by Nakai evaluation.Results: All the patients were performed endoscopic decompression of the lateral recess and nerve root by removing the ventral part of the superior facet joint,the ligamentum flavum and the intervertebral disc.The decompression range was from the inferior edge of the upper pedicle to the superior edge of the lower pedicle.The nerve root was detected to have no compression and the pulse of nerve root returned to normal.The patient got ambulant on the operation day and discharged if he had no discomfort symptom.In the study,68 cases got follow up.The mean follow-up time was 12.1 months (6-63 months).The VAS at dif-ferent follow-up time points was improved relative to the baseline,and the difference was statistically significant (F=491.60,P<0.001).The ODI at different follow-up time points was improved relative to the baseline,and the difference was statistically significant (F=189.91,P<0.001).The excellent and good rates of Nakai evaluation were 79.4％ (excellent in 42 cases,good in 12 cases,fair in 10 cases and poor in 4 cases).The mean intraoperative blood loss was (49.29±11.86) mL.The mean operation time was (92.46±21.34) min.The mean ambulation time was 1.8 h.The mean discharge time was 2.3 days.Postoperative epidural hematoma was found in 1 case.Foot drop was found in 1 case.Second stage open surgery was performed in 6 cases.Conclusion: We can apply transforaminal endoscopic decompression for the patients of lumbar spinal stenosis who have unilateral nerve root irritation.Patients with transforaminal endoscopic decompression can get less surgical trauma,quick recovery and obtain good short-term outcome.

Polymethylmethacrylate augmentation of bone cement injectable cannulated pedicle screws was used to treat degenerative lumbar scoliosis with osteoporosis / 北京大学学报(医学版)

Objective:To describe the application of polymethylmethacrylate (PMMA) augmentation of cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis.Methods: Retrospective cohort study was used to compare cement injectable cannulated pedicle screws (CICPs) group with PMMA augmentation and control group with traditional method in the correction surgery for Lenke-silva level Ⅲ and level Ⅳ degenerative scoliosis cases with osteoporosis.Both groups were followed up for 1 year.The clinical results were assessed by visual analog scale (VAS) of pain on lumbar and lower limbers,Oswestry disability index (ODI) score and EuroQol-5 dimensions (EQ-5D) score.The coronal major curve Cobb angel in coronal plane and thoracic kyphosis Cobb angle,lumbar lordosis Cobb angle and sagittal vertical axis (SVA) in sagittal plane were tested in whole long spine X ray.The fusion rates were evaluated by lumbar X ray and dynamic X ray.Results: In this study 34 cases were enrolled,15 cases in CICPs group and 19 cases in control group.The general characteristics including age,gender,weight,height,BMI and BMD were without statistical difference between the two groups.There were (5.7±2.2)PMMA augmentation screws in CICPs group.The operation time,blood loss and blood transfusion were higher in CICPs group than in control group,but without statistical difference.Lumbar VAS,lower limbers VAS,ODI score and EQ-5D were all better in 1 month post-operation,6 months postoperation and 1 year postoperation than in preoperation in both groups.lumbar VAS scores of CICPs group in 6 months postoperation(CICPs group 3.1±1.3 vs.control group 4.4±1.4,P<0.01) together with lumbar VAS scores (CICPs group 3.3±1.0 vs.control group 5.2±1.4,P<0.01),ODI scores (CICPs group 22.7±17.2 vs.control group 31.4±18.5,P<0.01) and EQ-5D in 1 year postoperation (CICPs group 2.9±2.0 vs.control group 3.5±2.5,P<0.01)were lower than those of control group.The coronal major curve Cobb angels were all lower in 1 month postoperation,6 months postoperation and 1 year postoperation than in preoperation in both groups;thoracic kyphosis Cobb angle and lumbar lordosis Cobb angle were all higher in 1 month postoperation,6 months postoperation and 1 year postoperation than in preoperation in both groups.The coronal major curve Cobb angel was lower in CICPs group than that in control group in 1 year postoperation (CICPs group 17.6°±6.9° vs.control group 21.2°±7.2°,P<0.01)and thoracic kyphosis Cobb angle was higher in CICPs group than that in control group in 6 months postoperation (CICPs group-33.5°±8.8 °vs.control group-28.9°±8.3°,P<0.01)and 1 year postoperation(CICPs group-33.0°±8.1° vs.control group-26.3°±7.4°,P<0.01) together with lumbar lordosis Cobb angle were higher in CICPs group than that in control group in 1 year postoperation(CICPs group 26.4°±8.1° vs.control group 22.1°±7.3°,P<0.01).Conclusion: Polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis was effective and safe,the short-term clinical result was good.

Clinical research of percutaneous vertebroplasty or percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures induced by glucocorticosteroid / 北京大学学报(医学版)

Objective:To investigate the clinical characteristics of vertebral compression fracture ( VCF) in glucocorticosteroid-induced osteoporosis ( GIOP) and risk of vertebral refracture after percuta-neous vertebroplasty ( PVP) or percutaneous kyphoplasty ( PKP) .Methods:In the study, 570 cases who received PVP or PKP as treatments of VCF from January 2010 to December 2013 were retrospective re-viewed, of which 42 were GIOP and 21 were followed up as GIOP group, and the other 528 were primary osteoporosis and 391 were followed up, of which 84 were selected as Control group based on age and gen-der.The fracture location, ratio of single segment fracture and multiple segments fracture in the two groups were compared.In the final follow up, the reoperation rates for vertebral refractures by the Kap-lan-Meier method in the two groups were compared.Results:The follow up periods were (24.0 ±13.1) months in GIOP group and (25.8 ±14.4) months in control group(P>0.05).In GIOP group, there were 11 cases with one-segment fracture, 2 with two-segments fracture, 3 with three-segments fracture, 2 with four-segments fracture, 2 with five-segments fracture and 1 with eight-segments fracture.In Control group, there were 67 cases with one-segment fracture, 12 with two-segments fracture, 3 with three-seg-ment fracture, and 2 with four-segments fracture.The ratio of single segment fracture in GIOP group was significantly lower than that in Control group(52.4% vs.79.8%,P=0.01).There were 50 fracture segments in GIOP group and 109 fracture segments in Control group.The ratios of fracture segments loca-ted in thoracic segments(T1-T10), thoracolumbar segments(T11-L1)and lumbar segments(L2-L5) were 18%, 46%and 36% in GIOP group and 11.9%, 58.7% and 29.4% in Control group ( P >0.05).The refracture rate in GIOP group was higher than that in control group (23.8%vs.6.0%).The survival rate was lower in GIOP group than that in control group ( Pthoracic segments>lumbar segments).The risk of multiple segments VCF was higher in GIOP than in primary osteoporosis. The risk of vertebral refractures after PVP or PKP was higher in GIOP than in primary osteoporosis.

Effect of polylactic acid-polyglycolic acid copolymer/collagen type Ⅰ microspheres combined with BMSCs on bone defects in osteoporotic rats / 中华骨科杂志

Objective To evaluate the bone repair capacity ofpolylactic acid-polyglycolic acid copolymer (PLGA)/collagen type Ⅰ (CoI) microspheres combined with BMSCs after being injected in intertrochanteric bone defect of osteoporotic female rats.Methods Prepared PLGA microspheres.The microspheres were coated with Col.BMSCs of the third passage were cultured with PLGA/CoI microspheres.Forty 3-month-old female SD rats were ovariectomized to establish osteoporotic animal models.The osteoporotic rats were randomly divided into 5 groups,including SHAM group,PBS group,Cell group,MS group and Cell+ MS group.There were 8 rats in each group.Different material was injected into the intertrochanteric bone defect site which was made with electric drill.Four rats of each group were sacrificed at 1 month and 3 months post-operation.The fenora were taken to measure the intertrochanteric bone mineral density (BMD) with DEXA and evaluate trabecular stucture with Micro CT.Results After 7 days of coculture,BMSCs seeded on PLGA/CoI microspheres had nice adherance and proliferation.There was no difference of BMC and BMD among all groups at 1 month post-operation.Tb.Th of Cell+MS group was higher than that of PBS group and MS group at 1 month post-operation.％Tb.Ar of Cell+MS group was higher than that of Cell group and MS group at 1 month post-operation.Tb.Sp of Cell+MS group had a tendence to decrease compared with other groups but there was no statistical difference at 1 month post-operation.After 3 months of operation,the BMC of Cell+MS group had a tendence to increase compared with that of PBS group and MS group but showed no statistical difference.BMD and Tb.Th of Cell+MS group was higher than those of other groups.％Tb.Ar of Cell+MS group was higher than that of SHAM group and PBS group.Tb.Sp of Cell+MS group had a tendence to reduce compared with other groups but showed no statistical difference.Conclusion The bone defect of osteoporotic site can be repaired 1 month after the injection of the PLGA/CoI microspheres combined with BMSCs.The trabecular reconstruction and bone quality of osteoporotic site can be improved 3 months after the injection.

Relationship between paravertebral vascular leakage and pulmonary cement embolism during percutaneous vertebroplasty / 中国组织工程研究

BACKGROUND:Percutaneous injection of bone cement into the vertebral body can enhance the vertebral strength and vertebral stability, and obtain pain relief. But the bone cement may leakage into the paravertebral vessels during injection, and may back to the right ventricle and flow into the pulmonary artery through vena cave and thus causing pulmonary embolism. OBJECTIVE:To evaluate the relationship between cement paravertebral vascular leakage and pulmonary cement embolism during percutaneous vertebroplasty. METHODS:Total y 134 cases of osteoporotic compression fractures treated with vertebroplasty were retrospectively analyzed. Among them, 23 cases of cement paravertebral vascular leakage were considered as the experimental group, and the 43 cases without cement paravertebral vascular leakage and had the complete imaging data were considered as the control group. The spine and chest X-ray films were taken before and after vertebroplasty to detect whether there were cement paravertebral vascular leakage and pulmonary cement embolism in the patients of two groups. RESULTS AND CONCLUSION:Among the 134 patients, 23 patients had cement paravertebral vascular leakage, and accounted for 17.2%. Among the 23 patients with cement paravertebral vascular leakage, three cases had pulmonary cement embolism without chest symptoms, and accounted for 13%. No pulmonary cement embolism occurred in the 43 patients without paravertebral vascular leakage of the control group, and there was no significant difference between two groups (P=0.039). Although the patients with cement pulmonary embolism remained asymptomatic, pulmonary cement embolism remained possible if cement paravertebral vascular leakage was detected during vertebroplasty.

Causes for kyphosis after removal of internal fixators for thoracolumbar vertebrae burst fractures / 中华创伤杂志

Objective To retrospectively analyze whether the kyphosis exists after removal of the internal fixators for thoracolumabar vertebrae fractures. Methods A total of 18 patients (35-68 years old) with thoracolumabar vertebrae fractures (T11-L2 ) were fixed with short segment pedical screw. The fixators were removed one year postoperatively to observe the changes of the Cobb' s angle and trauma vertebra'height. Results All the patients were followed up for 6-24 months ( average 18.7 months),which showed no intraoperative or postoperative complication, breakage or loosening of the screws. Compared to the Cobb angle and the vertebra height before removal of the internal fixators, the average loss of the Cobb angle was 0.7° and that of the vertebra height was 0.8 mm six months after removal of the fixators, 1.9° and 1.1 mm respectively one year after removal of the fixators, and 2.4° and 1.3 mm respectively two years after removal of the fixators in 16 patients without osteoporosis (P ＞0. 05). Among two patients with osteoporosis, the average loss of the Cobb angle and the vertebra height was 6° and 8°respectively and 3 mm and 5 mm respectively six months after removal of the fixators; 13° and 17° respectively and 5 mm and 7 mm respectively one year after removal of the fixators; 15° and 19° respectively and 6 mm and 7.5 mm two years after removal of the fixators. Conclusions After the internal fixation for thoracolumbar vertebrae burst fractures, kyphosis develops mildly, with insignificant change of the vertebral height. While the kyphosis becomes worse after removal of the fixators for thoracolumbar vertebrae burst fractures in patients with osteoporosis.

B-twin expandable spinal spacer for treatment of degenerative disc disease A 30-case retrospective analysis / 中国组织工程研究

A total of 30 patients with degenerative disc disease underwent posterior lumbar interbody fusion (PLIF) using a B-twin expandable spinal spacer (ESS) at the Department of Orthopedics,First Hospital,Peking University between August 2005 and February 2008 and were retrospectively analyzed.These patients consisted of 14 males and 16 females and averaged 28-72 years old.PLIF was performed at L1/2 in 1 patient,at L2/3 in 1 patient,at L3/4 in 1 patient,at L4/5 in 14 patients,and at L5/S1 in 13 patients.Patients underwent PLIF using simple B-twin ESS (n=8,1 employing single spacer,and 7 a pair of spacers) or B-twin ESS combined with pedicle screw (n=22,17 employing single placer,and 5 a pair of placers).B-twin ESS with a diameter of 9.5-11.0 mm was used in 28 patients and with a diameter of 11.5-13.0 mm in 2 patients.Examinations were carried out before surgery,post surgery,and during follow-up.Clinical symptoms were assessed using a 29-point Japanese Orthopaedic Association (JOA) score rating system.Spinal dysfunction was evaluated using the Oswestry Disability Index (ODI).The intervertebral space height and slippage reduction were measured through X-ray images.Twenty-eight of thirty patients were averagely followed up for 9 months.The excellent and good rate of ODI was 97% post surgery and 100% during follow-up period.The excellent and good rate of JOA was 93% post surgery and 96% during follow-up period.The proportion of intervertebral space height in upper vertebra that averaged 0.29±0.09 before surgery increased to 0.44±0.09 post surgery and stabilized at 0.4±0.09 upon final follow-up.The slippage was 10%-60% of upper vertebra before surgery,0%-40% post surgery,and 0%-30% till final follow-up.No neurological impairment or infection was found.There was 1 patient suffering from dural tear for adherence during decompression,1 patient presenting implant subsidence into the endplate post surgery,and 1 patient exhibiting spacer fragmentation during follow-up period.All outcomes indicate that B-twin ESS is characterized by minimal invasion,short surgery time,and less neurostimulation and provides satisfactory postoperative and follow-up efficiency.Attention should be paid to selecting suitable spacer type according to preoperative and intraoperative measurements.There is a breakage possibility if the spacer is put on one side of the space.To avoid this,sufficient bone graft is essential and two spacers may be put in one vertebra space if necessary.