Tranexamic acid dosage for spinal surgery: a meta-analysis.

PURPOSE: We conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of different doses of intravenous tranexamic acid (TXA) in spinal surgery. METHODS: We searched relevant academic articles from PubMed, Embase, the Cochrane Library, and CNKI. Two reviewers independently selected studies, assessed quality, extracted data, and evaluated the risk of bias. RevMan 5.4 was used for data analysis. RESULTS: Ten randomized controlled trials (RCTs) met the inclusion criteria and were identified, including 740 patients. According to the different dose regimens of intravenous TXA, the included studies' patients were divided into the high dose of intravenous TXA group and the low dose of intravenous TXA group. Compared with the low-dose group, the high-dose group can reduce the intraoperative blood loss (MD = - 100.87, 95% CI: [- 147.81, - 53.92], P < 0.0001). For the postoperative Hb and HCT, the high-dose group can separately maintain 4.54 g/dL (MD = 4.54, 95% CI: [2.08, 6.99], P = 0.003) and 1.27% (MD = 1.27, 95% CI: [0.59, 1.94], P = 0.0002). There were no statistically significant differences in total blood loss, preoperative Hb and HCT, operative time, and blood transfusion rate between the high-dose group and the low-dose group. CONCLUSIONS: Based on the present meta-analysis, compared with the low-dose of intravenous TXA in spinal surgery, the high dose of intravenous TXA decreases the intraoperative blood loss and preserves higher postoperative Hb and HCT levels without increasing the operative time and blood transfusion rate.

[Effects of HOXA1 Gene Antisense Oligonucleotides on Growth of Esophageal Cancer Cells].

OBJECTIVE: To investigate the effect of antisense oligodeoxynucleotides (ASODN) of Homeobox A1 gene ( HOXA1) on proliferation, apoptosis, invasion and migration of esophageal carcinoma cells. METHODS: The expression of HOXA1 protein in normal esophageal epithelial cells Het-1A and esophageal cancer TE-1, EC9706 and Eca109 cells was detected by Western blot. Screening of highly expressed of HOXA1 protein esophageal squamous cell carcinoma cells for follow-up experiments. HOXA1 antisense oligonucleotide (ASODN) chains, sense oligodeoxynucleotides (SODN) chain, and nonsense oligodeoxy nucleotides (N-ODN) chain were designed. The screened esophageal squamous cell carcinoma cells with high expression were divided into HOXA1 ASODN group (5, 10, 15 µmol/L HOXA1 ASODN transfected Eca109 cells), control group (conventional culture medium, no cell transfection), SODN group (cells transfected with 15 µmol/L of SODN) and N-ODN group (cells transfected with 15 µmol/L N-ODN). Cell viability, apoptosis rate and invasion and migration ability were detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, flow cytometry, transwell chamber respectively; The expression of HOXA1, phosphorylation serine/threonine kinase (p-AKT), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2) and B-cell lymphoma2 (Bcl-2) associated X protein (Bax) protein was detected by Western blot. RESULTS: Compared with normal esophageal epithelial cells Het-1A, the expression of HOXA1 protein in human esophageal squamous cell carcinoma cells TE-1, EC9706 and Eca109 was significantly higher ( P<0.05). The expression of HOXA1 protein was the highest in Eca109 cells, therefore, Eca109 cells were selected for follow-up experiments. The expression of HOXA1 protein in Eca109 cells transfected with HOXA1 ASODN was significantly decreased ( P<0.05). After transfection of Eca109 cells with HOXA1 ASODN, the viability of Eca109 cells decreased with the increase of concentration and time, the difference was significant compared with the control, SODN and N-ODN groups ( P<0.05). 15 µmol/L HOXA1 ASODN significantly inhibited cell viability. After 15 µmol/L HOXA1 ASODN was transfected into Eca109 cells, the invasion and migration abilities of cells were significantly decreased, the apoptosis rate was increased, the expressions of p-AKT, PCNA and MMP-2 were significantly decreased, and the expression of Bax was significantly increased ( P<0.05). CONCLUSION: Antisense oligodeoxynucleotides of HOXA1 gene can inhibit the proliferation, invasion and migration of esophageal cancer cells, and induce apoptosis. The mechanism is related to the inhibition of PI3K/AKT signaling pathway.

IL-16 regulates macrophage polarization as a target gene of mir-145-3p.

BACKGROUND: Interleukin 16 is an immunomodulatory chemokine that signals through CD4 + T cells, monocytes, macrophages and dendritic cells. Its expression in immune-related cells enhances the antimicrobial effect and inhibits HIV replication in macrophages. However, the role of IL-16 in macrophage polarization is uncertain. Mir-145 was reported to regulate IL-10 expression by targeting histone deacetylase 11 and promotes alternatively activated macrophage (M2) polarization. Mir-145 was also predicted to target IL-16 mRNA. We aimed to explore the roles of IL-16 and mir-145 in macrophage polarization and antimicrobial functions. METHODS: THP1 monocytes were employed in this study, and their cell activity when incubated with different concentrations of IL-16 was evaluated using the CCK-8 cell counting kit. To obtain polarized macrophages, THP-1 cells were induced by IL-4 and IL-13 following PMA incubation (M2 polarized macrophages) or induced by IFN-gamma and LPS (M1 classical macrophage activation). The influence of IL-16 on macrophage phagocytosis was quantified by the amount of chicken red blood cell phagocytized. IL-16, IL-10 and miR-145 expression in THP1 monocytes and induced macrophages was quantified by quantitative PCR. The miR-145 and IL-16 targeting relationship was verified by the dual luciferase reporter assay. The influence of IL-16 and mir-145 on macrophage polarization was evaluated by M1 and M2 macrophage characterized marker gene expression. RESULTS: The M0 macrophage subtype was induced by PMA. The M1 and M2 subtypes of macrophage were successfully induced by M1- and M2-specific induction. M1 macrophages express higher levels of IL-16 than M2 macrophages but express lower levels of IL-10 and mir-145 than M2 cells. IL-16 with a concentration up to 150 ng/mL has no influence on THP-1 cell proliferation but improves macrophage phagocytosis ability with the down-expression of IL-10 and up-expression of pro-inflammatory cytokines such as IL-1a and IL-6. Knockdown with its target siRNA is beneficial for macrophage maintenance but reduces phagocytosis ability. Mir-145 specifically targets the IL-16 3'UTR verified by the dual luciferase reporter assay. Mir-145 downregulates IL-16 expression and upregulates IL-10 expression, thereby promoting M2 macrophage polarization. CONCLUSION: IL-16 modulates macrophage polarization through regulating IL-10, IL-1a and IL-6 expression. Mir-145 is involved in M2 macrophage polarization by targeting IL-16 and enhancing IL-10 expression.

miR-10b promotes invasion by targeting KLF4 in osteosarcoma cells.

OBJECTIVE: Osteosarcoma is a common malignancy with high rate of metastasis. miR-10b has been reported to be expressed in many types of tumors abnormally and be associated with cancer carcinogenesis and progression. But the function of miR-10b in osteosarcoma is still unknown. So this study was aimed to investigate the role of miR-10b in osteosarcoma development. METHODS: miR-10b expression in osteosarcoma tissues and osteosarcoma cells were detected using real time PCR. The effects of miR-10b on osteosarcoma cells proliferation, apoptosis, migration and invasion were detected using CCK-8 assay, flow cytometry, wound-healing assay and transwell assay, respectively. The relationship between miR-10b and KLF4 was evaluated using dual-luciferase assay, correlation analysis. RESULTS: miR-10b was highly expressed in osteosarcoma tissues and osteosarcoma cells. Furthermore, inhibition of miR-10b in osteosarcoma cells depressed the cells proliferation, migration and invasion but promoted cells apoptosis. In addition, KLF4 was down-regulated by miR-10b and miR-10b expression was negatively related to KLF4 expression in osteosarcoma tissue, miR-10b participated in the process of osteosarcoma cells invasion by regulating KLF4 expression. CONCLUSION: miR-10b is overexpressed in osteosarcoma and KLF4 is the direct target gene of miR-10b. Furthermore, miR-10b promotes osteosarcoma cells progression by downregulating KLF4 expression. These results suggest that miR-10b functions as an oncomiR and play an important role in osteosarcoma cellular processes at least partially through regulating KLF4; miR-10b may be a therapeutic target for osteosarcoma treatment.

Treatment of Gustilo grade III leg fractures by external fixation associated with limited internal fixation.

OBJECTIVE: To explore the clinical effects of external fixation associated with limited internal fixation on treatment of Gustilo grade III leg fractures. METHODS: From July 2006 to December 2008, 40 cases of Gustilo grade III leg fractures were emergently treated in our unit with external fixation frames. Soft tissue injuries were grouped according to the Gustilo classification as IIIA in 17 cases, IIIB in 13 cases, and IIIC in 10 cases. All the patients were debrided within 8 hours, and then fracture reposition was preformed to reestablish the leg alignment. Limited internal fixation with plates and screws were performed on all the Gustilo IIIA cases and 10 Gustilo IIIB cases at the first operation. But all the Gustilo IIIC cases and 3 Gustilo IIIB cases who had severe soft tissue injuries and bone loss only received Vacuum-sealing drainage (VSD). Broad-spectrum antibiotics were regularly used and VSD must be especially maintained easy and smooth for one week or more after operation. Limited internal fixation and transplanted free skin flaps or adjacent musculocutaneous flaps were not used to close wounds until the conditions of the wounds had been improved. RESULTS: The first operations were completed within 90-210 minutes (170 minutes on average). The blood transfusions were from 400 ml to 1500 ml (those used for anti-shock preoperatively not included). All the 40 patients in this study were followed up for 6-28 months, 20.5 months on average. The lower limb function was evaluated according to the comprehensive evaluation standards of leg function one year after operation and the results of 28 cases were excellent, 9 were good and 3 were poor. CONCLUSION: External fixation associated with limited internal fixation to treat Gustilo grade III leg fractures can get satisfactory early clinical therapeutic effects.

Multi-slice spiral CT 3-dimensional reconstruction technique to treat multi-segmental degenerative spinal stenosis with traumatic instability of lower cervical spine.

OBJECTIVE: To study the feasibility of multi-slice spiral computed tomography (MSCT) 3-dimensional reconstruction technique in assisting cervical pedicle screw fixation (PSF) and double-door laminoplasty to treat multi-segmental degenerative spinal stenosis with traumatic instability (MDSTI) of lower cervical spine. METHODS: From September 2006 to August 2007, PSF combined with double-door laminoplasty was performed in 9 patients with MDSTI of lower cervical spine. MSCT 3-dimensional reconstruction techniques, including volume rendering (VR) and multi-planar reconstruction (MPR), were used to assist preoperative diagnosis and measurement to guide the procedure. MPR was performed after operation. In coronal view, the degree of screw perforation was measured precisely and the different positions of pedicle screws were divided into three grades according to Richter's method. In axial view, the canal sagittal diameter and transverse area of every laminoplasty level were measured. RESULTS: Nine patients with MDSTI of lower cervical spine underwent PSF (total 44 screws). According to the classification of Richter, 72.7% (32/44) was in Grade 1 and 27.3% (12/44) was in Grade 2. No screw perforation occurred in Grade 3 and no screw revision was done for misplacement. No iatrogenic damage was observed. Double-door laminoplasty was performed in total 42 volumes. The postoperative sagittal diameter and transverse area of cervical spinal canal were significantly increased (P<0.05). The confidence intervals of mean increased ratio were 23.43%-40.65% in sagittal diameter and 23.18%-42.07% in transverse area. Six months after laminoplasty, based on MSCT axial view, complete union between "open door" and allograft bone was obtained in 76.19% of volumes (32/42), and allograft bone was absorbed partly in 23.81% (10/42). A solid union in bilateral gutters was achieved in all cases. They were followed up from 6 months to 1 year (mean 7.8 months). Postoperative neural function recovery in two cases improved 2 ASIA grade, 5 cases improved 1 grade and 2 cases remained the same as preoperative grade. No cases had lower ASIA grade. CONCLUSION: Assisted with MSCT 3-dimensional reconstruction technique, PSF combined with double-door laminoplasty can be performed more safely and effectively to treat patients with MDSTI of lower cervical spine.

Gene expression profile related to inflammation in rat model of traumatic deep vein thrombosis.

OBJECTIVE: To study the relationship between inflammation and traumatic deep vein thrombosis (TDVT). METHODS: A rat model of deep venous thrombosis was established by directly clamping femoral vein. Based on the different biological situations of femoral vein thrombosis and observation phases, 150 SD rats were divided into 7 groups. Inflammatory cells in vein wall of each group were counted. The fold change and cluster analysis were applied to study the change of gene expression during the development of venous thrombosis. Especially, the genes related to inflammation, fibrinolysis, coagulation of endothelium were analyzed in detail. RESULTS: The inflammation cells in femoral vein wall were mostly neutrophilic granulocytes in Groups B, C and D, while they were lymphocytes in Groups E, F and G. Compared with Groups A, B, E and G, the inflammation cell counts in Groups C, D and F were much higher (P less than 0.05). The results of fold-change analysis showed that 2 504 genes (Log 2 ratio > or = 1 or < or = 1) presented different expressions in the process of TDVT. Most of these genes'functions were not clarified so far and the genes with known functions were involved in inflammation, DNA-dependent transcription regulation, blood coagulation, fibrinolysis, etc. Among them, 23 genes related to inflammation had different expressions during TDVT. The cluster analysis showed that the expression changes of several genes, such as IL-1 alpha, IL-1 beta, IL-6, Cinc2, corresponded with the development of femoral vein thrombosis. CONCLUSION: There is a close relationship between the genes related to inflammation and deep vein thrombosis induced by direct vascular trauma.

Application of spiral CT image 3D reconstruction in severe talar neck fracture.

OBJECTIVE: To explore the application of the spiral computerized tomography (CT) image three-dimensional (3D) reconstruction technique associated with the conventional radiography in the diagnosis and treatment of severe talar neck fracture. METHODS: Using the multi-slice spiral CT image 3D reconstruction technique, we analysed 11 cases of talar neck fracture. The fractures were reduced and fixed through a minimal incision and internal fixation with titanium cannulated lag screws. RESULTS: In the 11 cases, the results of CT image 3D reconstruction were in concordance with plain radiograph in 6 case of Hawkins type II. And the remaining 5 cases of Hawkins types III and IV could not be classified exactly only by radiographs, one of whom was misdiagnosed. After using the CT image 3D reconstruction, the 5 cases were classified exactly before osteosynthesis. The classifications of these 11 cases were confirmed finally by surgical findings. The duration of operation were 45-140 min, averaging 81 min (including the duration of C-arm fluoroscopy). X-ray exposure time was 6-58 seconds, averaging 22 seconds. The blood loss was less than 100 ml. The fracture union was achieved in 3 months. No nonunion, talus avascular necrosis or joint surface collapse occurred. Postoperative follow-up was from 1 to 25 months. According to Hawkins score, excellent result was found in 6 type II cases and 1 type III case; good result in 1 type III case with both medial and lateral malleolar fracture, 1 type III with medial malleolus fractures and 1 open type III; fair result in 1 open type IV with lateral malleolus fracture. CONCLUSIONS: By using the multi-slice spiral CT image 3D reconstruction associated with radiography to diagnose and treat severe talar neck fractures, the accuracy of diagnosis can be improved obviously. Based on this technique, more consummate operational plan can be designed and performed so as to achieve a better therapeutic effect.

Lower cervical spine injury treated with lateral mass plates and pedicle screws through posterior approach.

OBJECTIVE: To treat injury of the lower cervical spine C6 to C7 with cervical lateral mass plates and T1 pedicle screws through posterior approach. METHODS: The data of 8 patients with lower cervical spine C6 or C7 injury (6 patients with fracture and dislocation in C6 and C7 and 2 with fracture in C7) were analyzed retrospectively in this study. For the preoperative American Spinal Injury Association (ASIA) classification, Grade C was found in 3 cases and Grade D in 5 cases. Screws were placed on the lateral masses and the first thoracic pedicle with Margerl technique. Lamina or facet bone allografting was used to achieve a long-term stability. RESULTS: All the 8 patients were followed up for 5-37 months (mean: 15 months). No operative death occurred. There were no examples of aggravation of spinal cord injury or vertebral artery injury, cerebrospinal fluid leak, nerve roots injury, screw malposition or back-out, loose of alignment or implant failure. Clinical symptoms and ASIA classification were improved in all the patients. Postoperative MRI scanning confirmed the satisfactory screw placement in all the cases. CONCLUSIONS: Lateral mass plates and pedicle screws through posterior approach are safe and beneficial for patients with lower cervical spine C6 or C7 injury.

[The use of lateral mass screws and pedicle screws for the treatment of injury of lower cervical spine].

OBJECTIVE: To discuss the effect of the use of the cervical lateral mass plates screws and T(1) pedicle screws for the treatment of C(6) to C(7) injury through posterior approach. METHODS: There were 8 patients in the study group; Each of them had been injured with low cervical spine C(6) or C(7). There were 6 cases with C(6)-C(7) injury and 2 cases with C(7) injury. According to ASIA classification, 3 cases were in grade C and 5 cases in D. The lateral mass screws were placed on the lateral masses using Margel technique. Lamina or facet bone allografting were used to achieve a long-term stability. RESULTS: All 8 patients were followed up from 5 to 37 months (mean 15 months). No operative death occurred. There were no cord or vertebral artery injury, cerebrospinal fluid leak, nerve roots injury, screw malposition or back out, loose of alignment or implant failure. Clinical symptom and ASIA classification were improved in all patients. Postoperative MRI scanning confirmed satisfactory screw placement in all cases. CONCLUSION: This technique is safe and benefit to patients with low cervical spine C(6) or C(7) injury.