AIM:This study aims to explore the effects and underlying mechanisms of caloric restriction(CR)on folic acid(FA)-induced acute kidney injury(AKI)in mice.METHODS:An AKI model was established by in-traperitoneal injection of FA(250 mg/kg).(1)Twenty male C57BL/6J mice(20～25 g)were randomly assigned to 4 groups(n=5):sham+ad libitum(AL),FA+AL,sham+CR,and FA+CR.The mice in CR groups were subjected to a 66%reduction in daily food intake within a limited feeding window for 2 weeks,while those in AL groups had unrestricted access to food.All mice had free access to water,and their body weight changes were monitored throughout the experi-ment.(2)An additional set of twenty male C57BL/6J mice were divided into 4 groups(n=5):control,A769662,FA,and FA+A769662.The AMP-activated protein kinase(AMPK)agonist A769662(30 mg/kg)was administered intraperito-neally for 3 d prior to FA injection.(3)Modeling of tubule-specific AMPK knockout(RT-AMPK-CKO)mice followed the same protocol as wild-type C57BL/6J mice.Blood and kidney tissues were harvested 48 h after FA injection.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were measured using an automatic biochemical analyzer.The kidney pa-thology was examined by HE staining.The malondialdehyde(MDA)level and the reduced/oxidized glutathione(GSH/GSSG)ratio were assessed using assay kits.The protein levels of p-AMPK,AMPK,and ferroptosis-related markers were evaluated by Western blot and immunohistochemistry.RESULTS:(1)After 2 weeks,CR significantly reduced body weight and increased p-AMPK level compared with AL group(P<0.05).(2)Compared with FA+AL group,the mice in FA+CR and FA+A769662 groups exhibited notably lowered SCr and BUN levels,reduced expression of kidney injury mole-cule-1 and neutrophil gelatinase-associated lipocalin,lowered tubular injury scores,decreased long-chain fatty acid-CoA ligase 4(FACL4)and 4-hydroxynonenal levels,restored glutathione peroxidase 4(GPX4)expression,decreased MDA level,and enhanced GSH/GSSG ratio(P<0.05).(3)In the FA-induced renal injury model,RT-AMPK-CKO mice showed no significant differences compared with wild-type mice(P>0.05).However,in the FA+CR model,RT-AMPK-CKO mice failed to exhibit renal protection,with increased lipid peroxidation,elevated MDA level,and reduced GSH/GSSG ratio(P<0.05).Furthermore,CR-induced down-regulation of FACL4 and up-regulation of GPX4 were significantly reversed in RT-AMPK-CKO mice(P<0.05).CONCLUSION:The CR attenuates FA-induced AKI in mice by activating AMPK and inhibiting ferroptosis.

AIM:This study aims to explore the effects and underlying mechanisms of caloric restriction(CR)on folic acid(FA)-induced acute kidney injury(AKI)in mice.METHODS:An AKI model was established by in-traperitoneal injection of FA(250 mg/kg).(1)Twenty male C57BL/6J mice(20～25 g)were randomly assigned to 4 groups(n=5):sham+ad libitum(AL),FA+AL,sham+CR,and FA+CR.The mice in CR groups were subjected to a 66%reduction in daily food intake within a limited feeding window for 2 weeks,while those in AL groups had unrestricted access to food.All mice had free access to water,and their body weight changes were monitored throughout the experi-ment.(2)An additional set of twenty male C57BL/6J mice were divided into 4 groups(n=5):control,A769662,FA,and FA+A769662.The AMP-activated protein kinase(AMPK)agonist A769662(30 mg/kg)was administered intraperito-neally for 3 d prior to FA injection.(3)Modeling of tubule-specific AMPK knockout(RT-AMPK-CKO)mice followed the same protocol as wild-type C57BL/6J mice.Blood and kidney tissues were harvested 48 h after FA injection.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were measured using an automatic biochemical analyzer.The kidney pa-thology was examined by HE staining.The malondialdehyde(MDA)level and the reduced/oxidized glutathione(GSH/GSSG)ratio were assessed using assay kits.The protein levels of p-AMPK,AMPK,and ferroptosis-related markers were evaluated by Western blot and immunohistochemistry.RESULTS:(1)After 2 weeks,CR significantly reduced body weight and increased p-AMPK level compared with AL group(P<0.05).(2)Compared with FA+AL group,the mice in FA+CR and FA+A769662 groups exhibited notably lowered SCr and BUN levels,reduced expression of kidney injury mole-cule-1 and neutrophil gelatinase-associated lipocalin,lowered tubular injury scores,decreased long-chain fatty acid-CoA ligase 4(FACL4)and 4-hydroxynonenal levels,restored glutathione peroxidase 4(GPX4)expression,decreased MDA level,and enhanced GSH/GSSG ratio(P<0.05).(3)In the FA-induced renal injury model,RT-AMPK-CKO mice showed no significant differences compared with wild-type mice(P>0.05).However,in the FA+CR model,RT-AMPK-CKO mice failed to exhibit renal protection,with increased lipid peroxidation,elevated MDA level,and reduced GSH/GSSG ratio(P<0.05).Furthermore,CR-induced down-regulation of FACL4 and up-regulation of GPX4 were significantly reversed in RT-AMPK-CKO mice(P<0.05).CONCLUSION:The CR attenuates FA-induced AKI in mice by activating AMPK and inhibiting ferroptosis.

Objective To investigate the role and mechanism of growth differentiation factor (GDF) 15 in ischemia-reperfusion injury (IRI) during kidney transplantation. Methods Nine wild type donor mice and 9 wild type recipient mice were selected. The renal graft of 3 recipient mice were harvested at 4, 24 and 72 h after transplantation. GDF family transcriptome analysis was carried out, and the expression of GDF15 in renal tissues of each group were detected. Five wild type donor mice, 5 GDF15 knockout donor mice and 10 wild type recipient mice were selected. According to the experimental scheme, the mice were divided into wild type sham operation group, wild type transplantation group, GDF15 knockout sham operation group and GDF15 knockout transplantation group. Serum and renal tissue samples were extracted 72 h after transplantation. The renal function, renal tubular injury, inflammatory cell infiltration, inflammatory factors, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB expression level were compared in each group. Nine wild type donor mice, 9 GDF15 knockout donor mice and 18 wild type recipient mice were selected. According to the experimental scheme, the mice were divided into wild type transplantation group and GDF15 knockout transplantation group, and the survival rate of two group after kidney transplantation was observed. Results Transcriptome sequencing of renal graft tissues indicated that GDF15 was the most up-regulated GDF family gene, which was mainly expressed in renal tubules. Compared with the sham operation group, the renal function of mice was declined in the transplantation group. Compared with the wild type transplantation group, the serum creatinine and blood urea nitrogen levels of mice were significantly up-regulated in the GDF15-knockout transplantation group (both P < 0.05). The 1-week survival rate of mice was 87.6% in the wild type transplantation group and 41.8% in the GDF15 knockout transplantation group. In the GDF15 knockout transplantation group, the expression level of kidney injury molecule (KIM)-1 was up-regulated, and the renal tubule injury score was increased. In the wild type transplantation group, the renal tubules were dissolved or necrotized, and tubular formation was seen in the extramedullary and cortex area, whereas tubular necrosis and tubular formation were more evident in the GDF15 knockout transplantation group. The expression levels of myeloperoxidase (MPO) and F4/80 were up-regulated in the transplantation group, and the inflammatory cell infiltration was aggravated in the GDF15 knockout transplantation group. Compared with the sham operation group, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the transplantation group were up-regulated. Compared with the wild type transplantation group, the expression levels of TNF-α, IL-1β and IL-6 were also up-regulated in the GDF15 knockout transplantation group (all P < 0.05). In the transplantation group, the expression levels of TLR4 and NF-κB in the renal graft tissues were higher than those in the sham operation group. In the GDF15 knockout transplantation group, the expression levels of TLR4 and NF-κB in the renal graft tissues were higher compared with those in the wild type transplantation group. Conclusions GDF15 may alleviate the IRI of renal graft probably via inhibiting the TLR4-NF-κB signaling pathway.

Objective:To explore different surgical treatment options and effect for intraspinal cement leakage after percutaneous vertebroplasty (PVP).Methods:A retrospective case series study was carried out to analyze the clinical data of 5 patients with intraspinal cement leakage after PVP for osteoporotic vertebral compression fracture (OVCF) admitted to People's Hospital of Shanxi between May 2016 and January 2020, including 1 male and 4 females, with the age of 65-82 years [(75.4±7.5)years]. Injured segments were located at T 12-L 1 in 1 patient, L 1 in 1, L 2-4 in 1, L 3 in 1 and L 4-5 in 1. The American Spinal Injury Association (ASIA) classification was grade C in 2 patients and grade D in 3. Muscle strength was grade II in 2 patients and grade III in 3. The leakage of bone cement in the spinal canal was strip or columnar in 3 patients, leaning to one side of the spinal canal and adjacent to the nerve root, and the bone cement was removed by transforaminal endoscope for decompression. The leakage of bone cement in the dura mater and spinal canal was found in 2 patients. The intradural bone cement leakage was removed by durotomy, and the bone cement in the spinal canal was removed by transpedicular osteotomy, bone graft fusion and internal fixation. The visual analogue scale (VAS), Oswestry dysfunction index (ODI), ASIA grade and muscle strength were observed before operation, at 3 days, 3 months after operation and at the last follow-up. Results:All patients were followed up for 12-16 months [(13.6±1.8)months]. The VAS was significantly decreased at postoperative 3 days, 3 months and at the last follow-up [(2.6±0.6)points, (2.1±0.3)points, (1.9±0.5)points] when compared to (7.1±1.5)points before operation ( P<0.01). However, the VAS had no statistical difference at different time points after operation ( P>0.05). The ODI was 42.4±10.2, 25.6±6.0 and 21.4±3.6 at postoperative 3 days, 3 months and at the last follow-up, significantly different from that before operation (74.2±7.3) ( P<0.05 or 0.01). However, the ODI had no statistical difference at postoperative 3 months and at the last follow-up ( P>0.05). Two patients with preoperative ASIA grade C recovered to grade D and 3 patients with preoperative grade D recovered to grade E at the last follow-up ( P<0.05). Two patients could walk without crutches with muscle strength improved from grade II preoperatively to grade IV at the last follow-up ( P<0.01). Three patients had completed recovery of neurological function with muscle strength improved from grade III preoperatively to grade V at the last follow-up ( P<0.01). Conclusions:For OVCF patients with intraspinal canal cement leakage and neurological symptoms after PVP, if the bone cement is located on one side of the spinal canal and adjacent to the nerve root, the bone cement should be removed by foraminal endoscope for decompression; if the cement leakage occurs in the dura mater, the dura mater should be cut to remove the bone cement for decompression, which can effectively relieve pain and promote functional recovery.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective To evaluate the factors related to contralateral hip fracture in the elderly patients with hip fracture by meta analysis.Methods Pubmed,Cochrane,CBMdisc,CNKI Chinese Journal Full Text Database and Wan Fang Database were searched for publications at home and abroad from January 2005 to April 2018 on factors related to contralateral hip fracture after hip fractures in the elderly.The publication quality was strictly evaluated before the data were extracted concerning gender and age(＞ 65years) of the patients,concomitant osteoporosis (Singh sign ≥ 4),primary fracture type,concomitant Parkinson disease,concomitant stroke,concomitant senile dementia,concomitant cataract,concomitant rheumatoid arthritis,concomitant diabetes,type of internal fixation for primary fracture and therapeutic compliance.Revman5.0 was used to perform the statistical analysis and the OR value and 95％ CI were calculated fore each index.Results A total of 17 studies were included involving 1,504 patients with contralateral hip fracture among 13,717 elderly patients with hip fracture.The factors related to the refracture of the contralateral hip were the age of the patients (OR ＝-3.55,95％ CI:-5.60 ～-1.50,P ＜ 0.001),osteoporosis (OR=2.38,95％CI:1.36～4.17,P=0.002),Parkinson disease (OR=4.54,95％CI:2.74～7.53,P ＜0.001),stroke (OR=0.33,95％ C I:0.18～0.59,P ＜ 0.001),senile dementia (OR=0.43,95％CI:0.29～0.62,P ＜0.001),cataract (OR=0.37,95％CI:0.22～0.63,P ＜0.001),rheumatoid arthritis (OR =0.32,95％ CI:0.21 ～ 0.50,P ＜ 0.001),diabetes (OR =0.65,95％ CI:0.47～0.91,P=0.01),type of internal fixation for primary fracture (OR=0.51,95％ CI:0.30 ～ 0.85,P =0.01),and therapeutic compliance (OR =0.36,95％ CI:0.21 ～ 0.64,P ＜ 0.001).However,the refracture of the contralateral hip was not related to gender (OR =1.07,95％ CI:0.45 ～2.56,P=0.88),smoking (OR=0.86,95％CI:0.40～1.86,P=0.70),fracture type (OR=0.97,95％ CI:0.60～1.57,P=0.90),or hypertension (OR=0.70,95％ C I:0.41～1.21,P=0.20).Conclusions In elderly patients with hip fracture,the risks for contralateral hip fracture may be advanced age,concomitant osteoporosis,Parkinson disease,stroke,senile dementia,cataract,rheumatoid arthritis and diabetes,type of internal fixation for primary fracture,and poor therapeutic compliance.However,no sufficient evidence has suggested that gender,smoking,type of hip fracture or concomitant hypertension might be associated with the contralateral hip fracture.

Objective To observe the expression of parathyroid hormone - related peptide (PTHrp) receptor in tibial growth plate and its effects on tibial extension in chronic renal insufficiency rats. Methods Two-week-old male Sprague-Dawley rats were randomly divided into sham group, model group and enalapril group, each with 20 rats. In model group and enalapril group rats had chronic renal insufficiency induced by left ureteral obstruction, and rats were respectively given saline and enalapril by gavage after the operation. In sham group, left ureter was only exposed without ligation, and rats were given saline. The urine was collected 4 weeks after the operation and the total protein content was measured. Then all rats were killed. The concentrations of PTHrp, creatinine and urea nitrogen in intracardiac blood were detected. HE staining and Masson staining were performed on the left kidney to observe pathological changes of glomeruli and renal tubules. The total length of bilateral tibia was measured. The number of columnar cells in the growth plate proliferative zone was measured by safranin O staining and the expression of PTHrp receptor in the growth plate was detected by immunohistochemistry. Results The 24 h urine total protein, creatinine and urea nitrogen in model group were higher than those in sham group (all P＜0.05), while these 3 renal functional parameters in enalapril group were lower than those in model group (all P＜0.05). In model group and enalapril group rats had higher blood concentrations of PTHrp than that in sham group (all P＜0.05), but blood PTHrp in enalapril group was lower than that in model group (P＜0.05). HE staining and Masson staining showed that in the model group rats had severe tubular dilation, inflammatory cell infiltration and the tissue fibrosis, while in enalapril group renal tubules slightly dilated and had a few inflammatory cell infiltration and tissue fibrosis. Compared with those in the sham group, in model group the tibia length, the chondrocyte number of column structure in the growth plate proliferative zone and the PTHrp receptor decreased (all P＜0.05). But in enalapril group those indexes increased than model group (all P＜0.05). Conclusions Chronic renal insufficiency rats had increased PTHrp concentration in the blood but decreased PTHrp receptors expression in tibial growth plate, which lead to their limited tibial extension.

Objective: To investigate the clinical effect of combined anterior and posterior approach revision on complex acetabular fractures. Methods: A retrospective case series study was performed on the clinical data of 21 patients with complex acetabular fractures who underwent failed surgery through single approach from June 2012 to June 2017. There were 16 males and five females, averagely aged 34.6 years (range, 24-45 years). According to Letournel-Judet classification, there were seven patients with transverse+ posterior wall fracture, five patients with anterior column+ posterior semi-transverse fracture, four patients with double column fracture and five patients with "T" fracture. The first operation was performed by ilioinguinal approach in nine patients and by Kocher-Langebeck (K-L) approach in 12 patients. Revision surgery was performed using a combined anterior and posterior approach. The operation time and intraoperative blood loss were recorded, and the fracture healing was observed. The quality of fracture reduction was assessed according to Matta reduction criteria, and hip function by the modified D Aubigne and Postel score. The complications during and after operation were recorded. Heterotopic ossification was evaluated according to Brooker's criteria. Results: The patients were followed up for 12 to 36 months, with an average of 27 months. The operation time ranged from 180 to 360 minutes, with an average of 270 minutes. Intraoperative bleeding was 1 000-3 800 ml, with an average of 2 000 ml. Fractures were healed, with the healing time ranging from 3.5 to 7 months, with an average of 5 months. According to Matta reduction criteria, there were eight patients with anatomical reduction, 12 with satisfactory reduction and one with unsatisfactory reduction. The improved D Aubigne and Postal score was (11.1±1.9)points preoperatively and (15.6±1.7)points six months after operation (P<0.05), the outcome of hip function was excellent in three patients, good in 14, fair in three, and poor in one, with the excellent and good rate of 81%. There were three patients with transient injury of sciatic nerve, one patient with traumatic arthritis and one with heterotopic ossification of Brooker II. No femoral head necrosis or deep venous thrombosis in the lower extremities was found. Conclusion For complex acetabular fractures, combined anterior and posterior approach revision can promote fracture reduction, fracture healing, and functional recovery, with low incidence of complications.

Objective To evaluate the risk factors related to the failure of internal fixation for intertrochanteric fracture in Chinese patients.Methods A comprehensive Meta analysis of the clinical research from January 2005 to August 2016 on the failure of internal fixation for intertrochanteric fracture in Chinese patients was conducted after Pubmed,CNKI,Wanfang Data,et al.,had been searched.Revman5.0 was used to perform the heterogeneity test and calculate the OR value and 95％ CI after quality assessment and retrieval of the qualified data.Results Included for this analysis were 23 studies involving 4,031 patients of whom 588 failed.The factors related to the failure of internal fixation for intertrochanteric fracture included patient age [OR =0.51,95％ CI (0.30,0.90),P ＜ 0.05],osteoporosis [OR =1.91,95％ CI (1.05,3.47),P ＜0.05],fracture pattern[OR=0.23,95％ CI (0.18,0.30),P ＜0.05],quality of fracture reduction [OR =0.25,95％ CI (0.17,0.35),P ＜0.05],tip-apex distance (TAD) [OR =0.13,95％ CI (0.05,0.32),P ＜0.05],time for full weight bearing [OR=5.32,95％ CI (1.71,16.57),P ＜ 0.05],and associated internal diseases [OR =3.76,95％ CI (1.19,11.91),P ＜0.05].The relationship was not determined between the failure of internal fixation for intertrochanteric fracture and the following factors:gender [OR=0.78,95％ CI (0.54,1.11),P ＞ 0.05],injury cause [OR=1.68,95％ CI (0.66,4.25),P＞ 0.05] or type of internal fixation [OR=0.37,95％CI (0.06,2.14),P＞0.05].Conclusions High age,concomitant osteoporosis,complicated fracture pattern,unsatisfactory fracture reduction,TAD ≥ 25 mm,time for full weight bearing ＜ 6 weeks,and concomitant internal diseases may be the risk factors closely related to the failure of internal fixation for intertrochanteric fracture in Chinese patients.There has been no sufficient evidence to show that gender,injury cause or type of internal fixation may be associated with the failed internal fixation for intertrochanteric fracture.

Objective To identify the risk factors for the fractures secondary to percutaneous vertebroplasty for osteoporotic vertebral compression fractures.Methods A comprehensive search was conducted for the studies from January 2006 to September 2016 on the risk factors for secondary fractures after percutaneous vertebroplasty in the Cochrane Library,PubMed Data,CNKI,Chinese Biomedical Database,Wanfang Data and manually as well.After retrieval of the eligible data,software Revman5.0 was used to perform the heterogeneity test and calculate the pooled odds ratio (OR),weighted mean difference(WMD) value and 95％ confidence interval (CI).Results Twenty studies involving 3,602 patients,627 of whom had fracture secondary to the surgery,were included in this meta-analysis.Meta-analyses showed the secondary fracture after percutaneous vertebroplasty for osteoporotic vertebral compression fracture was related to bone mineral density [WMD =-0.66,95％ CI (-0.97,-0.36),P ＜ 0.05] and kyphosis after primary operation [WMD =4.51,95％ CI (3.02,6.00),P ＜ 0.05],but not to gender [OR =0.98,95％ CI (0.77,1.25),P＞ 0.05],age [WMD=1.48,95％CI (-0.13,3.09),P＞ 0.05],body mass index [WMD=-0.76,95％ CI(-1.61,0.08),P＞ 0.05],cement volume [WMD=-0.15,95％CI (-0.60,0.30),P＞0.05],intradiscal cement [0R=1.11,95％CI (0.56,2.22),P＞0.05],number of vertebrae primarily treated [OR=0.74,95％ CI (0.09,6.45),P ＞ 0.05],thoracolumbar spine [OR =0.86,95％ CI (0.63,1.18),-P ＞ 0.05],or cement injection approach [OR =1.58,95％ CI (0.74,3.37),P ＞ 0.05].Conclusions Bone mineral density and kyphosis after primary operation may be the risk factors closely correlative to the secondary fracture after percutaneous vertebroplasty.There has not been enough evidence to support the associations between the secondary fracture and gender,age,body mass index,cement volume,intradiscal cement,number of vertebrae primarily treated,thoracolumbar spine,or cement injection approach.