Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway / 中华医学杂志(英文版)

BACKGROUND@#Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23.@*METHODS@#We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.@*RESULTS@#DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown.@*CONCLUSIONS@#Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.

Clinical effect of dual growth rod technique in the treatment of early-onset scoliosis / 中华骨科杂志

Objective:To investigate the clinical efficacy of dual growing rods (DGR) in the treatment of early onset scoliosis (EOS), and to evaluate the safety of its clinical application.Methods:From March 2015 to August 2021, a total of 20 EOS patients with onset age within 10 years old who were treated with dual growth rod technique were retrospectively analyzed, including 8 males and 12 females. The mean age of patients at first surgery was 9.0±1.4 years (range, 6.3-10.8 years); the preoperative Cobb angle was 59.0°±16.8° (range, 41.2°-103°). The Cobb angle, thoracic kyphosis angle, lumbar lordosis angle, T 1-T 12 height, T 1-S 1 height, coronal plane imbalance, sagittal vertical axis (SVA), apical vertebral translation (AVT) and Campbell's space available for lung ratio (SAL) were recorded and analyzed while surgery-related complications were also recorded. Results:The average follow-up time of 20 patients was 28.07±14.30 months. The average initial hospital stay was 20.56±8.28 days, the average initial operation time was 211.70±39.80 min, the average blood loss in the initial operation was 255.00±149.50 ml, and the average surgical distraction was 1.60±0.51 times per person. The Cobb angle of the main curve in the coronal plane decreased from 59.00°±16.80° before operation to 33.40°±11.80° after the initial operation, which was 29.67°±11.67° at 1 year and 29.40°±11.30° at the last follow-up. Preoperative thoracic kyphosis angle was 41.39°±6.06°, decreased to 31.72°±3.56° after the initial operation, was 30.32°±4.26° at 1-year and 30.24°±4.23° at the last follow-up; preoperative lumbar lordosis angle was 45.90°±8.03°, decreased to 42.65°±9.05° after initial operation, 41.55°±7.84° at 1-year follow-up, and 41.53°±8.21° at the last follow-up; preoperative T 1-S 1 height was 31.76±4.42 cm, initial after operation, it increased to 34.64±3.96 cm, 36.73±3.87 cm at 1 year, and 37.28±4.36 cm at the last follow-up; preoperative T 1-T 12 height was 17.38±2.76 cm. increased to 19.39±2.86 cm after the initial operation, 21.77±2.71 cm at 1 year, and 21.91±2.74 cm at the last follow-up; Preoperative coronal balance was 1.52±0.73 cm, and decreased to 0.87±0.38 cm after the initial operation, 0.81±0.38 cm at 1 year, and 0.77±0.37 cm at the last follow-up; preoperative sagittal balance was 1.94±0.78 cm, and 1.42±0.56 cm after operation, 1.28±0.55 cm at 1 year, and 1.26±0.57 cm at the last follow-up; The preoperative apical vertebra offset was 4.33±1.85 cm, and 2.16±1.47 cm after the initial operation, 1.63±1.17 cm at 1 year, and 1.61±1.23 cm at the last follow-up; SAL increased from preoperative 0.88±0.05 to 0.94±0.03 postoperatively, and 0.96±0.01 at 1-year follow-up, and 0.97±0.01 at the last follow-up. The differences between the above indicators before and after surgery were statistically significant ( P<0.05); there was a statistically significant difference in SAL between the 1-year follow-up and the last follow-up ( t=3.80, P=0.001), and other indicators were not statistically significant. Among the 20 cases, there were 5 cases of postoperative complications, including 2 cases of pedicle screw loosening and displacement, 2 cases of transverse process hook decoupling, and 1 case of proximal junctional kyphosis (PJK). The complication rate was 25% (5/20), all of them underwent revision treatment, and the prognosis was good after timely treatment. Conclusion:The dual growth bar technique can effectively control the progression of EOS deformity, preserve the longitudinal growth potential of the spine, and buy time for the development of the thorax in children, which has high safety.

Surgical strategy selection and clinical outcome analysis in treatment of congenital cervicothoracic scoliosis / 中华骨科杂志

Objective:To investigate the surgical strategy of posterior correction of cervicothoracic scoliosis in children and adolescents, and to analyze the curative effect of surgical correction.Methods:A retrospective study was conducted on 14 patients with cervicothoracic scoliosis who underwent surgical treatment in the department of spine surgery of our hospital from January 2014 to June 2020, including 9 female and 5 male patients. 8 patients were treated with Halo traction before surgery.Among them, 7 patients were treated by posterior column osteotomy and fusion surgery, 7 patients were treated byposterior approach hemivertebra osteotomy. The scoliosis Cobb angle, T 1 tilt angle, clavicle angle, neck tilt angle, shoulder height difference, sagittal balance distance, coronal balance distance and local kyphosis angle were measured compared among before operation, after operation, at 1 year follow-up and at the last follow-up to evaluate the effect of surgical treatment and the correction loss at follow-up. Intraoperative and postoperative complications were recorded, and the Scoliosis Research Society question naires-22 (SRS-22) questionnaire was completed preoperatively and at 24-month follow-up to evaluate the functional status and treatment effect. Results:All 14 patients successfully completed the operation, the operation time was 6.85±1.79 h (range, 5-11 h); the intraoperative blood loss was 685.71±265.61 ml (range, 400-1 200 ml), and the follow-up time was 37.28±13.75 months (range, 24-72 months). The Cobb angle of the main curve was 50.20°±15.19° preoperatively, 10.91°±6.46° postoperatively , 10.53°±6.42° at 1-year follow-up, and 10.14°±5.95° at the last follow-up, and the difference was statistically significant ( F=45.55, P<0.001), the preoperative and postoperative difference was statistically significant ( t=10.62, P<0.001) with a correction rate of 78.32%±11.41%. The T 1 inclination angle was 16.08°±8.06° before operation, 3.71°±2.40° after operation, 4.05°±1.94° at 1-year follow-up, and 3.97°±2.04° at the last follow-up, and the difference was statistically significant ( F=10.55, P=0.001), the preoperative and postoperative difference was statistically significant ( t=6.37, P<0.001) with a correction rate of 69.56%±25.86%. The neck tilt angle was 7.45°±3.72° before operation, 2.45°±1.12° after operation, 2.75°±0.89° at 1-year follow-up, and 3.10°±2.01° at the last follow-up, and the difference was statistically significant ( F=6.65, P=0.008), in which postoperative correction rate was 57.92%±25.41%, and the difference was statistically significant ( t=4.69, P<0.001). The data of shoulder height difference before operation did not conform to normal distribution (Shapiro-Wilk test, P=0.017), it was 0.97 (0.54, 1.32) cm before operation and 0.53±0.40 cm after operation, and the postoperative correction rate was 50.17%±27.38%, the difference was statistically significant ( Z=3.18, P=0.001). The total score of SRS-22 questionnaire was increased from 4.21±0.29 preoperatively to 4.81±0.17 at 24-month follow-up ( t=7.35, P<0.001). Except for one patient with transient upper limb numbness, the other 13 patients showed no obvious intraoperative or postoperative complications. Conclusion:Both posterior column osteotomy with fusion and posterior hemivertebra osteotomy are effective in the treatment of cervicothoracic scoliosis, and the surgeon can make individual treatment plans according to different conditions.

Clinical study of deformed complex vertebral osteotomy (DCVO) in the treatment of angular kyphosis of cured spinal tuberculosis / 中华骨科杂志

Objective:To evaluate the feasibility and clinical efficacy of deformed complex vertebral osteotomy (DCVO) technique on the treatment of angular kyphosis of cured spinal tuberculosis.Methods:A retrospective study was performed on patients with angular kyphosis of cured spinal tuberculosis who underwent the DCVO technique or posterior vertebral column resection (PVCR) technique from Jan, 2007 to Jan, 2019. 33 patients were included, 18 males and 15 females, the average age was 39.5±15.0 years old (ranged 9-78 years old). The vertebral deformity in thoracic vertebrae 14 cases, thoracolumbar vertebrae 16 cases, and lumbar vertebrae 3 cases. 20 cases underwent the DCVO technique, while 13 cases underwent PVCR technique. For DCVO group, the multiple malformed vertebrae were considered a malformed complex, and a larger range and angle wedge osteotomy was performed within the complex using the DCVO technique. PVCR technique would resect the whole deformed vertebrae, and subsequently brought the two separated spinal columns together with instruments and titanium mesh. The intro-operative blood loss, operating time and complications were recorded. The radiological measurements included preoperative and postoperative spinopelvic parameters, which including thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and segmental kyphosis. The recovery of neurological function was evaluated by Frankle classification.Results:All patients were followed up for 7-72 months. Comparing with the cases underwent PVCR technique, the DCVO group has a significantly lower blood loss (1315.00±462.57 ml), operating time (293.00±83.86 min) and complications rate (1.5%). At the time of preoperation, postoperation and last follow-up, the deformity angle of DCVO group was 96.80°±6.32°, 29.10°±6.96°and 29.05°±6.49°, which gained an average 69.9% correction rate. The statistical analysis suggested that deformity angle was enormously corrected. And there was an insignificant difference between DCVO group and PVCR group. Meanwhile, the preoperative, postoperative and follow-up TK of DCVO group was 96.96°±29.13°, 37.15°±4.88° and 37.00°±3.89°respectively, whosecorrection rate was 67.1%; LL was 66.70°±21.21°, 42.25°±5.53° and 41.90°±4.98°, which have a significant difference between pre-operation and post-operation/follow-up ( F=23.997, P<0.001) ; SVA was 75.95±18.63 mm, 16.30±6.88 mm and 16.55±7.30 mm. PI was 47.50°±6.12°, 47.35°±5.54°and 47.90°±5.93°, PT was 37.25°±9.63°, 18.50°±1.99° and 19.00°±1.65°; SS was 10.25°±8.27°, 29.15°±5.91° and 28.85°±5.77°. The sagittal and spinopelvic parameters of two groups improved significantly at postoperation and follow-up. No obviously difference of spinal parameters was found between two groups at preoperation and postoperation. Both groups have cases with dysneuria. And all of these cases achieved different degrees of recovery at follow-up. Conclusion:The use of DCVO technique for the treatment of post-tubercular angular kyphosis is safe and efficiency. DCVO leads a better clinical outcomes and lower complication rate than VCR technique.

Expanding PSO technique for the treatment of congenital severe thoracic angular kyphotic deformity / 中华骨科杂志

Objective To evaluate the clinical efficacy and feasibility of using the expanding pedicle subtraction osteotomy (E-PSO) technique for the treatment of congenital severe thoracic angular kyphotic deformity.Methods We retrospectively reviewed a cohort of 13patients with congenital severe kyphosis admitted to our hospital from January 2010 to June 2015 including 5 males and 8 females,the average age is (34.9±20.5) years old (ranged 15-55 years old).The vertebral deformity in T7～83 cases,T8～93 cases,T9～102 cases,T10～114 cases,T9～111 case.All cases were treated by E-PSO technique.The multi-malformed vertebrae are considered as a complexus.And the osteotomy was performed within the complexus.The superior and inferior endplate of the complexus were reserved.After the osteotomy was completed,alternately pressed tightly closed the upper and lower parts.Results All cases were followed up for 10-42 months,with an average of 32 months.At the time of preoperation,postoperation andthe last follow-up,the deformity angle was 107.0°±3.5°,23.5°± 1.5° and 23.5°±0.2°;TK was 98.1°±7.6°,28.9°±3.0° and 29.5°±0.1 °,LL was 94.1 °± 1.5°,43.7°± 1.3° and 44.1 °±5.3°;SVA was (-0.6±39) mm,(1.6±7.9) mm and (6±0.7) mm,respectively;PI was 28.9°±1.6°,31.7±12.3°and 31.9°±2.1°;PT was 17.7°±1.9°,13.4°±3.4°and 13.1°±4.2°,SS was 11.3°±0.4°,18.2°±1.1° and 18.7°±2.1°,respectively.The sagittal parameters and spinopelvic parameters except SVA were significantly improved in the post-operation and the last follow-up compared with the pre-operation according to the image data.No significant loss of correction occurred during the follow-up,and there was no statistical difference.The preoperative VAS score was (5.7± 1.4) points,ODI score was (19.8±12.7) points.The last follow-up VAS score was (1.9±0.7) points,the ODI score was (9.2±0.7) points.No case of nerve damage,infection and other complications,and no dissection,displacement and rupture of internal fixation were found during the follow-up.Conclusion The use of E-PSO technique for the treatment of congenital severe thoracic kyphotic kyphosis is feasible and can achieve better curative effect.

Silencing of estrogen receptor beta gene influences the expressions of transforming growth factor beta1 and bone morphogenetic protein 2 in human osteoblasts / 中国组织工程研究

BACKGROUND:There are few studies concerning estrogen receptorβgene, and its mechanism of regulating the bone metabolism is stil unclear now. OBJECTIVE:To analyze the effect of estrogen receptorβ(ERβ) silencing on the expressions of transforming growth factorβ1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) in human osteoblasts METHODS:There were three groups:blank control group (hFOB 1.19 uninfected with any retrovirus);negative control group (containing invalid interference fragment ERβ-shRNA-nc);optimal RNAi group (ERβ-shRNA-3). ERβ-shRNA retroviral vectors in the optimal RNAi group were used to transfect human osteoblasts fol owed by resistance screening and cel expansion. MTT assay was used to detect the proliferative activity of ERβ-silenced osteoblasts. Then under estrogen intervention, the stable inhibition rate of ERβwas determined using western blot assay, and the expressions of TGF-β1 and BMP-2 in human osteoblasts after ERβsilencing were detected by RT-PCR technology and western blot assay. RESULTS AND CONCLUSION:Human osteoblasts that were stably transfected by ERβ-shRNA-3 retroviral vector was selected successful y, and ERβsilencing had no significant influence on the cel proliferation (P>0.05). Under the interference of estrogen, the silencing efficiency of ERβprotein was (93.11±0.57)%(P<0.05), and after ERβsilencing, the expressions of TGF-β1 and BMP-2 were increased by (26.65±3.81)%and (16.62±1.71)%at mRNA level, and increased by (23.79±3.76)%and (18.08±3.20)%at protein level (both P<0.05). In conclusion, ERβmay play an important role in bone metabolism by regulating the expressions of TGF-β1 and BMP-2.

Clinical practice of an endocrinology clinical pharmacists participating in the treatment of a patient with diabetes and hyperprolactinemia / 药学实践杂志

Objective To explore the working pattern for endocrinology clinical pharmacists participating in clinical drug treatment .Methods By participating in the treatment for a patient with diabetes and hyperprolactinemia and analyzing the cau‐ses of poor glycemic control and hyperprolactinemia ,clinical pharmacists proposed therapeutic regimen .Results The long‐term psychotropic medication may be one of the reasons why blood glucose of the patient was unsatisfactorily controlled .The patient with hyperprolactinemia may be associated with her longstanding use of paliperidone .The patient was recommended to consult a psychiatrist and switch to an alternative medication which does not cause hyperprolactinemia .Conclusion The active partici‐pation of clinical pharmacists during clinical drug therapy could improve the medication rationality and compliance of patients with drugs .

Silenced estrogen receptor beta affects the expressions of osteoprotegerin and receptor activator of nuclear factor-kappa B ligand in osteoblastic MG63 cells / 中国组织工程研究

BACKGROUND:Studies concerning how estrogen receptorβparticipates in bone metabolism are few now. OBJECTIVE:To investigate the effect of estrogen receptorβon the expression of osteoprotegerin and receptor activator of nuclear factor-κB ligand in human osteblast-like cells. METHODS:The retrovirus with the most effective interference sequence and non-specific short hairpin RNA was used to transfect human osteoblast-like cellMG63 in order to screen out the stable colon, and then amplified and cultured. The blank control and non-specific short hairpin RNA were used as control, and the stable inhibition rate of estrogen receptorβwas detected. The 17β-estradiol was added into the cells in three groups, that were MG63 cells, short hairpin RNA retrovirus estrogen receptorβ-mediated MG63 cells and negative control short hairpin RNA retrovirus-medicated MG63 cells, in order to detect the expressions of osteoprotegerin and receptor activator of nuclear factor-κB ligand mRNA in human osteoblast-like cells. RESULTS AND CONCLUSION: The human osteoblast-like MG63 cellline was further stably transfected with pRNAT-H1.4/Retro-estrogen receptorβshort hairpin RNA3, and then compared with the blank control and negative control, and found that estrogen receptorβcould express the stable inhibited human osteoblast-like cellline. The inhibition rate of estrogen receptorβmRNA was (88.17±1.17)%(P<0.05), and the inhibition rate of estrogen receptorβprotein was (89.01±1.22)%(P<0.05), indicating that estrogen receptorβgene knockdown human osteoblast-like cellmodels were constructed successful y. After estrogen intervention for 48 hours, the inhibition of MG63 cells with estrogen receptorβcould up-regulate the osteoprotegerin mRNA and protein expression in the blank control group and the negative control group (P<0.05), down-regulate the receptor activator of nuclear factor-κB ligand mRNA and protein expression (P<0.05), and up-regulate the osteoprotegerin receptor activator of nuclear factor-κB ligand expression. The results indicate that estrogen receptorβmay play an important role in bone metabolism through regulating osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.

Serum monocyte chemoattactant protein-1 level and spinal tuberculosis susceptibility / 中国组织工程研究

BACKGROUND:The monocyte chemoattactant protein-1 gene polymorphism is associated with spinal tuberculosis susceptibility. OBJECTIVE:To investigate the association between serum monocyte chemoattactant protein-1 expression level and spinal tuberculosis susceptibility in Han population of Hunan province. METHODS:The patients with spinal tuberculosis and the healthy volunteers were recruited in Xiangya Hospital of Central South University from December 2004 to December 2010. The empty peripheral venous blood 2 mL were col ected from the subjects in early morning, then the monocyte chemoattactant protein-1-362 genotypes were detected by polymerase chain reaction and DNA sequencing technology. And the serum monocyte chemoattactant protein-1 level was detected by enzyme linked immunosorbent assay technology. The ROC curve was used for diagnostic tests to calculate diagnostic threshold value of serum monocyte chemoattactant protein-1 level to spinal tuberculosis susceptibility, and to analyze the diagnostic titer. RESULTS AND CONCLUSION:208 patients with spinal tuberculosis and 210 healthy volunteers were included. The serum monocyte chemoattactant protein-1 level of the spinal tuberculosis patients was significantly higher than that of the healthy volunteers [(134.58±51.63) ng/L vs. (39.18±17.45) ng/L, P<0.01]. The serum monocyte chemoattactant protein-1 level could not be affected by gender, but over-expressed in patients with monocyte chemoattactant protein-1-362-CC genotypes. The serum monocyte chemoattactant protein-1 level higher than 101.65 ng/L indicated that the patients might suffered from spinal tuberculosis (sensitivity:85.5%, specificity:94.3%, Youden index:0.799, area under curve of ROC:0.946, 95%confidence interval:0.916-0.975, P<0.01). The serum monocyte chemoattactant protein-1 level may be associated with spinal tuberculosis susceptibility in Han population of Hunan province, highly expressed serum monocyte chemoattactant protein-1 can be used as one of the indicators for the diagnosis of spinal tuberculosis.

Risk factors of iatrogenic spinal cord injury during cervical or thoracic spinal surgery / 中华创伤杂志

ObjectiveTo find out the risk factors causing iatrogenic spinal cord injury (ISCI) so as to provide theoretical support for reducing the spinal cord injury during spinal operation. Methods A retrospective study was done on 120 patients undergone cervical or thoracic spinal( C1-T12 ) surgery at Xiangya Hospital of Central South University from January 2002 to January 2009. The patients were randomly divided into injury group (n = 34) and control group (n = 86) and the univariate analysis was used to analyze 30 factors including clinical factors, iconography factors, operation and pathology factors as well as possible protective factors. Then, the factors with statistical difference were analyzed by using the multi-factor unconditioned Logistic analysis.Results The univariate comparison between the two groups showed statistical difference ( P ＜ 0. 05 ) in nine factors including combined hypertension, combined diabetes mellitus, preoperative ASIA grade, spinal canal stenosis rate, ratio of spinal cord area/efficient area of vertebral canal, spinal cord MRI T2WI high signal, bleeding amount during operation, intraspinal prominence adhesion to dura mate of spinal cord as well as intraoperative use of methylprednisolone. The multi-factor Logistic regression analysis revealed that ASIA grade, value of spinal cord area/efficient area of vertebral canal, spinal cord MRI T2W1 high signal and bleeding amount in operation had positive correlation with ISCI. Use of methylprednisolone during operation had negative correlation with ISCI. ConclusionsCombined diabetes mellitus, ASIA grade, spinal cord MRI T2W1 high signal, ratio of spinal cord/vertebral canal area and bleeding amount in operation are the risk factors for ISCI. Use of large dose methylprednisolone exerts preventive effect on ISCI.

The correlative factors affected the early clinical efficiency of surgical management of lumbar disc degeneration / 中国医师杂志

Objective To explore the correlative factors that affected the early clinical efficacy of surgical management of lumbar disc herniation.Method 208 cases of lumbar disc herniation were recruited since December 2007.The details of their therapy in different periods were compared and analyzed.Result The aggressive discectomy was the most powerful factor related to the better early clinical outcome.The patients with preoperative JOA score ＞ 17 were associated to the poor clinical outcome.The patients with postoperative JOA score ≥ 25 on 3 month and ≥ 24 on 1 year after operations were associated to better early clinlcal outcome.Conclusion The pre- and post-operative JOA score and aggressive discectomy were the factors affected the clinical outcome.