Objectives:To observe the osteogenic properties and sustained release of 3D printed nano-hydroxyapatite(nHA)artificial bone loaded with a novel triple anti-tuberculosis drug combination(PaMZ)of Pretomanid(Pa),Moxifloxacin(M),Pyrazinamide(Z)and bone morphogenetic protein 2(BMP-2)in vivo.Methods:40 New Zealand rabbits were divided into four groups randomly and constructed spinal bone defect models.Group A(experimental group)implanted with 3D-printed PaMZ/BMP-2-loaded nHA artificial bone;group B(negative control group)implanted with blank nHA artificial bone;group C(positive control group)implanted with autologous iliac bone;group D(blank group)without bone grafting.The general conditions were observed,body temperature,weight,and liver and kidney function were monitored.The bone defect restoration was observed by spiral CT 3D reconstruction at the 4th,8th and 12th week postoperatively and was evaluated with CT-Hedberg scale;the gross observation of tissues and histopathological observation of the implants-bone defect interface were carried out at the 8th and 12th week postoperatively.100 SD rats were divided into two groups randomly,experimental group implanted with 3D-printed PaMZ/BMP-2-loaded nHA artificial bone,control group implanted with blank nHA artificial bone.The drug concentrations in the plasma and muscle tissue around the material at different time points was tested with high performance liquid chromatography.Results:All animal models were successfully constructed without incision infection or death.The body temperature,weight and liver and kidney function indexes of the experimental groups in the rabbit models were normal,with no statistical differences from those of the control groups(P＞0.05).The CT-Hedberg score showed that there was no statistical difference between group A and group C at the 4th,8th and 12th week(P＞0.05),however,there was statistical difference between all the other groups at different time points(P＜0.05).The observation of the gross specimens at the 12th week after surgery showed that the artificial bone in group A was completely encapsulated or replaced by new bone,but there was still some artificial bone exposed in group B.Quantitative analysis of the total trabecular area at the implant-bone defect interface showed no statistical difference between groups A and C at the 8th and 12th week postoperatively(P＞0.05),and a statistical difference between the remaining groups(P＜0.05).No drug components were detected in the SD rat model control group,the three drugs Pa,M,Z in experimental group can be sustained-released in local tissues for at least 84d.The blood drug concentration was not detected at the initial time point after local implantation of the drug-loaded artificial bone,and the subsequent measured results were much lower than the local tissue drug concentration,and the two had a positive correlation.Conclusions:The 3D printed PaMZ/BMP-2-loaded nHA artificial bone has good osteogenic properties in vivo,the effect of restoring spinal bone defects is comparable to that of autologous iliac bone,which is better than that of HA artificial bone scaffold alone.Its sustained release behavior in vivo is satisfactory,and the blood drug concentration is much lower than the local tissue drug concentration.

Objective: To investigate the value of small incision approach in the anterior surgery of thoracic and lumbar spinal tuberculosis. Methods: A clinical data of 65 patients with thoracic or lumbar spinal tuberculosis treated with posterior-anterior surgery between January 2015 and January 2018 was retrospectively analyzed. The patients were divided into small incision group (group A, 29 patients) and traditional incision group (group B, 36 patients) according to the length of anterior incision. There was no significant difference in general data such as gender, age, disease duration, segment of lesion, American Spinal Cord Injury Association (ASIA) grading, preoperative pain visual analogue scale (VAS) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Cobb angle of spinal kyphosis between 2 groups ( P>0.05). The length of anterior incision, operation time, intraoperative blood loss, postoperative complications, postoperative hospitalization time, ESR, and CRP were recorded and compared. The VAS score was used to evaluate the pain after operation. The Cobb angles in patients with spinal kyphosis were measured and the loss of angle and correction rate of angle were calculated. The result of bone graft fusion was assessed according to the Bridwell standard. Results: The length of anterior incision, operation time, intraoperative blood loss, and hospitalization time of group A were all significantly less than those of group B ( P<0.05). All patients in both groups were followed up 12-29 months (mean, 20 months). There were 4 cases (13.8%) and 14 cases (38.9%) of postoperative complications in groups A and B respectively, showing significant difference ( χ2=5.050, P=0.025). The ESR and CRP in 2 groups all returned to normal at 6 months after operation, and there was no significant difference in ESR and CRP between 2 groups at 3 months, 6 months, and last follow-up ( P>0.05). At last follow-up, the neurological function of patient with neurological symptoms was significantly better than that before operation, and there was no significant difference between 2 groups ( Z=0.167, P=0.868). The VAS scores of 2 groups at each time point after operation were significantly lower than those before operation ( P<0.05); the VAS score in group A was significantly lower than that in group B ( t=-2.317, P=0.024) at 1 day after operation, but there was no significant difference between 2 groups ( t=-0.862, P=0.392) at last follow-up. Among the patients with kyphosis, the Cobb angle was significantly decreased at 1 day after operation and last follow-up when compared with preoperative angle ( P<0.05); but there was no significant difference between 1 day after operation and last follow-up ( P>0.05). There was no significant difference in Cobb angle, loss of angle, and correction rate between 2 groups after operation ( P>0.05). The bone graft healed well at last follow-up in 2 groups. There was no significant difference in bone graft fusion rate between 2 groups at 6 months after operation, 1 year after operation, and last follow-up ( P>0.05). At last follow-up, all patients cured, and no recurrence occurred. Conclusion: In the anterior surgery of thoracic and lumbar tuberculosis, the application of small incision approach can achieve the similar effectiveness as traditional incision surgery with the advantages of minimally invasive, less complications, and quick recovery.

Objective:To determine the clinical efficacy of posterior intervertebral surgery for single-segment thoracolumbar spinal tuberculosis.Methods:Clinical data were retrospectively analyzed in 62 patients with thoracolumbar spinal tuberculosis who underwent posterior intervertebral surgery (A group) or posterior and anterior combined intervertebral surgery (B group) from January 2010 to January 2015 in Department of Spinal Surgery,General Hospital,Ningxia Medical University.The operative time,blood loss,length of hospital stay,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) level,neurological function,VAS score,vertebral Cobb angle,bone healing,and postoperative complications were compared between the 2 groups.Results:All patients were followed up for 10 to 30 (average 22) months after the operation.In the A group,operative time,blood loss,and hospital stay were less than those in the B group (P＜0.05).In the follow-up,the pain of patients was alleviated and nervous function was improved obviously in the 2 groups compared with pre-operation.The ESR and CRP at the 6 months after operation returned to the normal range in patients of the 2 groups.There were significant differences in the ESR and CRP among the pre-operation,the 6 months after operation,and the end of follow-up within the group (P＜0.05),while there were no significant differences in ESR and CRP between the 6 months after operation and the end of follow-up (P＞0.05).There were no significant differences in the ESR and CRP among the pre-operation,the 6 months after operation,and the end of follow-up in the 2 group (P＞0.05).The Cobb angles after the operation and the end of follow-up were significanthy smaller than those before the operation (P＜0.01),while there were no significant differences in Cobb angle before operation,after the operation,and the end of follow-up between the 2 groups (P＞0.05).There were no significant differences in the bone healing rate at 6 months or 1 year after operation between the A group and B group (P＞0.05) and the complication rate of the A group was lower than the B group (P＜0.01).Conclusion:Clinical efficacy of posterior intervertebral surgery is satisfatory in treating single-segment thoracolumbar spinal tuberculosis with less complications.

Objective To study the in vitro cytotoxicity of HRZ (isoniazid + rifampin + pyrazinamide) / transforming growth factor (TGF) β1 siRNA nanoliposomes on human macrophages and the underlying mechanism. Methods Self-made nanoliposomes were used to study with the cultured human macrophages in vitro. MTT assay was used to detect cell proliferation. Flow cytometry was used to analyze apoptosis and cell cycle. Electron microscopy was used to observe autophagy. RT-PCR and Western blot were employed to analyze the silenced expression of target gene TGF-β1. Results HRZ/TGF-β1 siRNA nanoliposomes (triple liposome) inhibited macrophage proliferation within certain range of concentration, and cell cycle was captured in G2 phase. The HRZ / TGF-β1 SiRNA nanoliposomes could significantly inhibit the expression of target gene TGF-β1 in human macrophages. Conclusions The self-made triple liposome has evident effect in silencing the target gene. It is a promising biomaterial, which meets the required specifications in terms of cytotoxicity.

Objective To investigate clinical efficacy of transforaminal approach debridement with fusion,thoracolumbar single segment of Brucella spondylitis pedicle screw fixation (TLIF surgery).Methods We analyzed retrospectively the clinical data of 28 patients with Brucella spondylitis treated in our department between January 2009 and January 2014 with TLIF surgery (Group A) and internal fixation with a simple posterior anterior interbody disease debridement,autogenous bone graft (Group B).The two groups were compared in operation time,blood loss,postoperative ambulation time,hospitalization days,erythrocyte sedimentation rate (ESR),Creactive protein (CRP),American Spinal Injury Association (ASIA) classification,visual analogue scale (VAS),Oswestry Disability Index (ODI),Cobb angle of vertebral bone graft healing,and complications.Results All the patients were followed up for an average of 20.2 months (18 to 27 months).They were all cured.Compared with those in Group B,patients in Group A had shorter operation time (164.60±59.19)min,significantly reduced blood loss (346.00±108.90)mL and complications (1 case);significantly shorter postoperative ambulation time (3.36±1.11 days),hospitalization days (17.36 ± 4.19) days and duration (13.16 ± 3.94) months (P ＜ 0.05).The two groups did not significantly differ in VAS scores,ODI,ESR CRP,or Cobb angle (P＞0.05).Conclusion On the basis of norms of anti-drug treatment for brucellosis,TLIF surgery on Brucella spondylitis has the advantages including less trauma,shorter operation time,easier operation,less bleeding,earlier postoperative ambulation,and lower complication rate.

BACKGROUND: Calcium sulfate/poly amino acid compound materials carrying triple anti-tuberculosis drugs have been proved to have excellent slow release performance based on our preliminary studies on the physical and chemical properties and the release properties of the compound materials.OBJECTIVE: To observe the slow release performance of the calcium sulfate/poly(amino acid) compound material carrying triple anti-tuberculosis drugs in a rabbit model of spinal tuberculosis.METHODS: Twenty-four New Zealand white rabbits were used to make L4-5 spinal tuberculosis models and divided into two groups in a random way following removal of tuberculosis lesions. Calcium sulfate/poly amino acid compound material carrying isoniazide, rifampicin, pyrazinamide or calcium sulfate/poly(amino acid)compound material with no drugs was implanted into the defect in the experimental or control group,respectively. At 2, 4, 6 and 8 weeks after implantation, the concentrations of isoniazid, rifampicin and pyrazinamide in the defect region, including the bone tissue, adjacent psoas major and inferior vena cava,were measured.RESULTS AND CONCLUSION: In the experimental group, the isoniazid levels in the damaged bone tissue and psoas major were kept in minimum bactericidal concentration (MBC) at 8 weeks after implantation and in the minimum inhibitory concentration (MIC) at the end of 12 weeks after implantation, while its level in the vein was kept in MBC at 2 weeks and in MIC at 8 weeks. The rifampicin levels in the bone tissue and psoas major were kept in MBC at 4 weeks after implantation and in the MIC at 8 weeks after implantation, while its level in the vein was kept MIC at 4 weeks.The pyrazinamide levels in the damaged bone tissue and psoas major were kept in MBC at 8 weeks after implantation and in the MIC until 8 weeks after implantation, while its level in the vein was kept MIC at 8 weeks. In the control group,there were no levels of isoniazid, rifampicin and pyrazinamide in the damaged bone tissue, adjacent psoas major and inferior vena cava in comparison with the baseline. These results show that isoniazid, rifampicin and pyrazinamide in the defect region can achieve sustained slow release in the rabbit model of spinal tuberculosis after implantation of the calcium sulfate/poly(amino acid) compound material carrying triple anti-tuberculosis drugs. In addition, the local drug concentration and duration in the defect region are better than those in the blood.

Objective To discuss the clinical efficacy of surgical treatment of pathologic vertebral surgery for thoracic and lumbar tuberculosis. Methods All of 322 cases of thoracic and lumbar spinal tuberculosis patients from December 2003 to June 2014 were retrospectively analyzed in our department. All patients were underwent debridement, fusion and nerve decompres?sion surgery. According to different fixed methods, patients were divided into pathologic vertebral surgery group (fixation complet?ed within lesions invaded motion unit) including 91 males and 100 females, with an average age of 41.53 years, and non?pathologic vertebral surgery group (long segments or short segment fixation) including 61 males and 70 females, with an average age of 42.72 years. We observed the tuberculosis cure rate, degrees of deformity, pain and neurological recovery, operative time, blood loss and complications by follow?up. Results The average follow?up time was 75.52 months in pathologic vertebral surgery group and 76.21 months in non?pathologic vertebral surgery group. The total number of pathologic vertebras in pathologic vertebral surgery group and non?pathologic vertebral surgery group were 277 and 218 respectively, and the average was 1.45 and 1.66. The total number of fixed segments was 277 in pathologic vertebral surgery group and 485 in non?pathologic vertebral surgery group, and the average fixed segments was 1.45 and 3.70. The cure rate was 85.86%in pathologic vertebral surgery group and 85.49%in non?pathologic vertebral surgery group at 6 months postoperatively, and 98.95%and 98.47%at the last follow?up time, with no signifi?cant difference between groups. Graft fusion rate was 89.00%in pathologic vertebral surgery group and 89.31%in non?pathologic vertebral surgery group 6 months postoperatively, 98.38%and 98.47%at the last follow?up time, without significant difference. In lumbar spine, the average correction of Cobb's angle was 12.4° in pathologic vertebral surgery group and 13.1° in non?pathologic vertebral surgery group, and the average angle loss was 1.3 and 1.4°, with no significant difference. In thoracolumbar, the average correction of Cobb’s angle was 10.9°in pathologic vertebral surgery group and 11.1°in non?pathologic vertebral surgery group, and the average angle loss was 1.7°and 1.5° respectively, without significant difference. However, in thoracic, the average correction of Cobb's angle was 10.2° in pathologic vertebral surgery group and 12.7° in non?pathologic vertebral surgery group, and the average angle loss was 3.6° and 2.5°respectively, with significant difference. The mean operation time was 210.45 min in pathologic verte?bral surgery group and 210.45 min in non?pathologic vertebral surgery group, with significant difference. The average blood loss was 726.12 ml in pathologic vertebral surgery group and 726.12 ml in non?pathologic vertebral surgery group, with significant dif?ference. The complication rate was 11.51%in pathologic vertebral surgery group and 11.45%in non?pathologic vertebral surgery group, with no significant difference. Conclusion Pathologic vertebral surgery surgery is a safe, effective and feasible method of operation for treatment of thoracic and lumbar tuberculosis, which can effectively preserve adjacent normal vertebral motion unit features. The thoracic surgery was less satisfactory than the lumbar and thoracolumbar surgery.

Objective To explore the compare of complete and incomplete radical debridement for thoracolumbar spinal tuberculosis.Methods Data of 296 patients with spinal tuberculosis from January 2000 to January 2011 were retrospectively analyzed.All patients were divided into two groups according to completeness of debridement:complete debridement group (group A) and incomplete debridement group (group B).There were 162 cases in group A including 86 males and 76 females,with an average age of 38.74± 17.26 years.There were 134 cases in group B including 73 males and 61 females,with an average age of 35.64± 18.21 years.All paticnts had undergone anterior debridement,focal graft implantation,anterior or posterior deformity correction,and internal fixation.Regular follow-up was required in the two groups.Results Residual sclerotic walls (36.54％),multipie cavities (34.62％),affected bony bridges (13.46％),sequestmm (3.37％),abscess (7.21％) and other lesionses (4.81％) were found in the group B.The first three factors were made up 84.62％ of the total.The mean follow-up time was 76.13±8.32 months in the group A and 79.24±5.49 months in the group B.The symptoms,C-reactive protein and erythrocyte sedimentation rate were improved more obviously in group A than those in group B.Six months after operation,tuberculosis healing rate in group A and group B was 29.01％ (47 patients) and 4.48％ (6 patients),respectively.The mean healing time was 4.36± 1.27 months in the group A and 9.15±2.53 months in the group B,with significant differences.The mean the time of chemotherapy was 5.21± 1.38 months in the group A and (10.45±2.15) months in the group B,with significant differences.Reoperation rate in group A and group B was 0.62％ (1/162) and 4.48％ (6/134),respectively.Conclusion Sclerotic bone,multiple cavities,and bony bridges are parts of foci in spinal tuberculosis.Clearing tuberculous foci with sclerotic bone,multiple cavities,and bony bridges can increase the curative effect,shorten the time of chemotherapy and reduce the side effects of drug,thus early resumption can be achieved.

BACKGROUND:Radiotherapy alone is not suitable for tumor-caused vertebral fractures and neurological dysfunction. In recent years, 125I radiation particles have been widely used in a variety of primary or secondary tumors and achieved good results. Percutaneous kyphoplasty can restore vertebral height efficiently, remodel spinal stability, and relieve pain.
OBJECTIVE:To evaluate safety and effectiveness of percutaneous kyphoplasty combined with 125I in patients with metastatic spinal tumors.
METHODS:A retrospective study was conducted to review 30 cases of metastatic spinal tumors undergoing percutaneous kyphoplasty combined with 125I from March 2011 to July 2012. Symptoms, signs, and imaging findings were col ected and analyzed. Al the patients had a refractoriness back pain. CT scan showed osteolytic changes in the vertebrae. The visual analogue scales, WHO standards for pain relief and Owestry disability index were recorded to analyze the clinical symptoms outcome and recovery of neurological function, and the change of height in abnormal vertebrae was measured. The fol ow-up time was 1 day, 1 month and 6 months postoperatively. RESULTS AND CONCLUSION:Operations in al the 30 patients were done successful y. Al patients got a conspicuous pain relief in 24 hours after operation, and nospinal injury or compression was found. There were significant differences in scores of visual analogue scales, pain levels, Owestry disability index, and the height of vertebral bodies before and after operation (P<0.05). During postoperative fol ow-up of 1 and 6 months, scores of visual analogue scales, pain levels, Owestry disability index, and the height of vertebral bodies showed no difference from those at 24 hours postoperatively (P>0.05). Bone cement leakage occurred in the anterior longitudinal ligament (n=2) and intervertebral space (n=2), and no serious complications occurred. Percutaneous kyphoplasty combined with 125I is a safe and effective way to treat metastatic spinal tumors, which can quickly ease the pain caused by spinal tumor, recover the abnormal vertebral height, reduce complications and improve life quality of patients.

Objective:To investigate the results of surgical treatment for multi-level spinal tuberculosis with focal debridement ,bone grafting and primary internal fixation.Method:27 cases of multi-level spinal tuberculosis treated by operation from January 1999 to January 2007 were reviewed retrospectively.3 vertebral bodies involved in 15 cases,4 vertebral bodies involved in 7 cases,5 vertebral bodies involved at least in 5 cases.Of these,there were 5 cases in thoracic vertebra,7 cases in lumbar vertebra,11 cases in thoracolumbar vertebra,4 cases in lumbosacral vertebra.11 cases showed neurological deficit before surgery,According to the Frankel classification,Frankel B in 1 case,Frankel C in 2,Frankel D in 8.The preoperative average Cobb angle of kyphosis was 35°±7° (range,26°-43°).The focal debridement,bone grafting and primary internal fixation were performed for all patients.Among these protocols, 16 cases underwent one staged posterior spinal internal fixation and anterior focal debridement,bone grafting.11 cases had anterior spinal internal fixation with focal debridement and bone grafting.All patients received anti-TB chemotherapy before and after operation.Anti-TB chemotherapy protocols consisting of combinations of rifampin,isoniazid,ethambutol and streptomycin were administered for 3 months which including 3 weeks before the operation and 3 months after the operation,followed by rifampin,isoniazid and ethambutol for a total of 9 months.The clinical outcomes were evaluated according to the criteria designed by WU Qiqiu et al.Result:The average surgical time was 240 minutes (range,150-300min),with the average intraoperative blood loss of 1000ml (range,600-1400ml),There was no complication such as nerve injury and cerebrospinal fluid leakage.The incision in 1 case presented sinus which had a secondary healing later on,others obtained primary healing.The average postoperative Cobb angle of kyphosis was 15°±5°(range,12°-20°).All cases were followed up for an average of 18 months(range, 14-48 months).The patients with paraplegia recovered to the normal in 8 months.Bony fusion was achieved in all cases with mean fusion period of 7 months(range,5-14 months) with no incidence of hardware failure.At the final follow-up,all patients had evidence of clinical heal and the solid bony fusion.Conclusion:Focal debridement,bone grafting and primary internal fixation is reliable in dealing with multi -level spinal tuberculosis.