Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study.

INTRODUCTION: Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). METHODS: A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse. RESULTS: Eighty-one patients (age, 25.0 years; interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p < 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment. CONCLUSION: Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.

TRPM2 protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction via modulating autophagy.

Background: Cisplatin is a widely used anti-tumor agent but its use is frequently limited by nephrotoxicity. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel which is generally viewed as a sensor of oxidative stress, and increasing evidence supports its link with autophagy, a critical process for organelle homeostasis. Methods: Cisplatin-induced cell injury and mitochondrial damage were both assessed in WT and Trpm2-knockout mice and primary cells. RNA sequencing, immunofluorescence staining, immunoblotting and flowcytometry were applied to interpret the mechanism of TRPM2 in cisplatin nephrotoxicity. Results: Knockout of TRPM2 exacerbates renal dysfunction, tubular injury and cell apoptosis in a model of acute kidney injury (AKI) induced by treatment with cisplatin. Cisplatin-caused tubular mitochondrial damage is aggravated in TRPM2-deficient mice and cells and, conversely, alleviated by treatment with Mito-TEMPO, a mitochondrial ROS scavenger. TRPM2 deficiency hinders cisplatin-induced autophagy via blockage of Ca2+ influx and subsequent up-regulation of AKT-mTOR signaling. Consistently, cisplatin-induced tubular mitochondrial damage, cell apoptosis and renal dysfunction in TRPM2-deficient mice are mitigated by treatment with a mTOR inhibitor. Conclusion: Our results suggest that the TRPM2 channel plays a protective role in cisplatin-induced AKI via modulating the Ca2+-AKT-mTOR signaling pathway and autophagy, providing novel insights into the pathogenesis of kidney injury.

STING promotes ferroptosis through NCOA4-dependent ferritinophagy in acute kidney injury.

Ferroptosis in tubules has been implicated in the pathogenesis of acute kidney injury (AKI), whereas the regulatory mechanism remains unclear. The stimulator of interferon genes (STING) is previously recognized as a critical mediator of innate immunity via a DNA-sensing pathway and has been increasingly linked to lipid peroxidation, a hallmark of ferroptosis. Herein we investigated the role and the underlying mechanism of STING in AKI models established by ischemia/reperfusion (IR) in C57BL mice. The expression level of STING was predominantly increased in tubules of kidney after IR treatment. Besides, STING deficiency markedly alleviated IR-induced lipid peroxidation, tissue damage and renal dysfunction. Consistently, in vitro experiments demonstrated that the increase in ferroptotic cell death, lipid ROS production and the decrease in GSH peroxidase 4 (GPX4) expression in renal tubular cells subjected to ferroptosis agonist or hypoxia/reoxygenation intervention were all mitigated by genetic deficiency or pharmacological inhibition of STING, while all exacerbated by STING overexpression. Further, these detrimental effects of STING overexpression relied on the induction of ferritinophagy, i.e. autophagic degradation of ferritin, leading to iron overload. Mechanistically, STING mediated the initiation of ferritinophagy through interacting with nuclear receptor coactivator 4 (NCOA4), a fundamental receptor for the transfer of ferritin into lysosome. Collectively, STING contributes to ferroptosis during ischemic AKI through facilitating NCOA4-mediated ferritinophagy and shows the potential as a promising therapeutic choice for AKI.

Mitophagy induced by UMI-77 preserves mitochondrial fitness in renal tubular epithelial cells and alleviates renal fibrosis.

Renal fibrosis is the final common outcome of chronic kidney disease (CKD), which remains a huge challenge due to a lack of targeted treatment. Growing evidence suggests that during the process of CKD, the integrity and function of mitochondria in renal tubular epithelial cells (TECs) are generally impaired and strongly connected with the progression of renal fibrosis. Mitophagy, a selective form of autophagy, could remove aberrant mitochondria to maintain mitochondrial homeostasis. Deficiency of mitophagy has been reported to aggravate renal fibrosis. However, whether induction of mitophagy could alleviate renal fibrosis has not been stated. In this study, we explored the effect of mitophagy activation by UMI-77, a compound recently verified to induce mitophagy, on murine CKD model of unilateral ureteral obstruction (UUO) in vivo and TECs in vitro. In UUO mice, we found the changes of mitochondrial damage, ROS production, transforming growth factor (TGF)-ß1/Smad pathway activation, as well as epithelial-mesenchymal transition phenotype and renal fibrosis, and these changes were ameliorated by mitophagy enhancement using UMI-77. Moreover, TEC apoptosis, nuclear factor (NF)-κB signaling activation, and interstitial inflammation after UUO were significantly mitigated by augmented mitophagy. Then, we found UMI-77 could effectively and safely induce mitophagy in TECs in vitro, and reduced TGF-ß1/Smad signaling and downstream profibrotic responses in TGF-ß1-treated TECs. These changes were restored by a mitophagy inhibitor. In conclusion, we demonstrated that mitophagy activation protected against renal fibrosis through improving mitochondrial fitness, downregulating TGF-ß1/Smad signaling and alleviating TEC injuries and inflammatory infiltration in kidneys.

Mannose-binding lectin activates the nuclear factor-κB and renal inflammation in the progression of diabetic nephropathy.

Increased serum mannose-binding lectin (MBL) level has been proven to correlate with the development of diabetic nephropathy (DN). Here, we aim to find the role and mechanism of MBL involved in the progression of DN. Patients with DN were recruited and divided into two groups according to different rs1800450 genotypes of the MBL2 gene, and inflammatory profiles in monocytes/macrophages were compared between the two groups. MBL was given to treat macrophages, HK2, and HMC, and a co-culture transwell system was then employed. Renal inflammation and fibrosis parameters were measured after knocking down or overexpressing MBL genes in mice. Proinflammatory profile, manifesting as enhanced IL-1ß production and M1 polarization, was found in monocytes/macrophages from DN with a rs1800450 GG genotype of MBL2 gene who had higher MBL level, compared with those with a rs1800450 GA genotype. In mechanism, MBL directly induced inflammatory responses in macrophages, which promoted inflammatory and fibrotic markers in HK2 and HMCs during co-culture. Further experiments showed that MBL can promote macrophages transforming to the M1 subset mainly by activating the nuclear factor-κB pathway. After downregulation of MBL, the blood glucose, triglyceride, urine protein, injuries of glomerulus and tubules, and the degree of renal inflammation and fibrosis were ameliorated in db/db mice treated with AAV-MBL1/2-shRNA. Overexpression of MBL promoted macrophage infiltration in the kidney. In conclusion, MBL is a crucial mediator in the progression of DN via activating the nuclear factor-κB pathway in macrophages. This will serve as a genetic base for some patients with DN who have poor outcomes and provide a direction for the screening.

The gut microbiome in microscopic polyangiitis with kidney involvement: common and unique alterations, clinical association and values for disease diagnosis and outcome prediction.

BACKGROUND: Microscopic polyangiitis (MPA) is an autoimmune disease characterized by frequent kidney involvement. Imbalance of intestinal flora has been found implicated in multiple immune-mediated disorders. However, the profiling and the role of the gut microbiome in MPA remains unclear. METHODS: We performed 16S rRNA amplicon sequencing on fecal samples from 71 MPA patients with kidney involvement (35 at incipient active stage, 36 at remissive stage) and 34 healthy controls (HCs). Microbial diversity and abundance were compared among the three cohorts. The correlation between altered microbes and clinical indices were investigated. Two random forest models based on the profiling of the gut microbiome were constructed for the diagnosis of MPA. RESULTS: Two α-diversity indices, including Simpson and Shannon index, were decreased in MPA patients (P<0.001), especially in those with active disease (P=0.001). ß-diversity analysis showed biased microbial composition among the three groups. Genus Actinomyces and Streptococcus were more abundant in both MPA cohorts than those in HCs, while genus Subdoligranulum, Eubacterium hallii, Ruminococcaceae UCG013, Eubacterium ventriosum, Dorea and Butyricicoccus were more abundant in HCs than those in both MPA cohorts. All the 6 genera with decreased abundance belong to short-chain fatty acids (SCFA)-producing taxons. Besides, 1 and 2 operational taxonomic units (OTUs) were enriched in patients with active MPA who needed dialysis at sampling and in patients who progressed to end-stage renal disease during follow up, respectively. Furthermore, the model for diagnosis of MPA incorporated 6 OTU markers and achieved an AUC of 93.45% (95% CI, 88.15-98.74%). Similarly, the model for predicting disease activity incorporated 11 OTU markers and achieved an AUC of 90.71% (95% CI, 82.49-98.94%). CONCLUSIONS: Alteration of intestinal flora existed in MPA patients with kidney involvement and was characterized by increased abundance of genus Actinomyces and Streptococcus and decreased abundance of 6 SCFA-producing genera. Gut microbial profiling combined with machining-learning methods showed potentials for diagnosing MPA and predicting disease activity.

Mitochondrial DNA-Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease.

The integrity and function of mitochondria are essential for normal kidney physiology. Mitochondrial DNA (mtDNA) has been widely a concern in recent years because its abnormalities may result in disruption of aerobic respiration, cellular dysfunction, and even cell death. Particularly, aberrant mtDNA copy number (mtDNA-CN) is associated with the development of acute kidney injury and chronic kidney disease, and urinary mtDNA-CN shows the potential to be a promising indicator for clinical diagnosis and evaluation of kidney function. Several lines of evidence suggest that mtDNA may also trigger innate immunity, leading to kidney inflammation and fibrosis. In mechanism, mtDNA can be released into the cytoplasm under cell stress and recognized by multiple DNA-sensing mechanisms, including Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signaling, and inflammasome activation, which then mediate downstream inflammatory cascades. In this review, we summarize the characteristics of these mtDNA-sensing pathways mediating inflammatory responses and their role in the pathogenesis of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. In addition, we highlight targeting of mtDNA-mediated inflammatory pathways as a novel therapeutic target for these kidney diseases.

The Clinicopathologic Characteristics and Complement Activation of Antineutrophil Cytoplasmic Antibody-associated Vasculitides With Glomerular IgA Deposition.

The renal injury caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by few or no immune deposits in glomerulus. A growing number of AAV patients with glomerular immunoglobulin (Ig)A deposits have been reported. We retrospectively investigated all AAV patients with glomerular IgA deposits diagnosed in our center. Serum galactose-deficient IgA1 (Gd-IgA1) level and glomerular Gd-IgA1 and IgA staining were measured. Moreover, we detected complement pathway components in their sera. A total of 168 AAV patients were enrolled, including 26 patients with glomerular IgA deposition and 142 patients with pauci-immune-complex deposition. The AAV patients with IgA deposition had a tendency of lower systemic disease activity, presenting with lower erythrocyte sedimentation rate, lower myeloperoxidase-ANCA, and tendency of lower C reactive protein and Birmingham Vasculitis Activity Score. For renal injury, there were no significant differences in clinical data, pathologic parameters, or renal outcome between groups. The serum level of Gd-IgA1 and intensity of glomerular Gd-IgA1 staining in IgA deposition AAV patients were similar to IgA nephropathy patients. All patients in the IgA nephropathy group and AAV groups with or without IgA deposition had the activation of the alternative complement pathway, whereas AAV patients with IgA deposition also had the activation of the classic complement pathway. Correlation analysis showed serum C1q level correlated directly with serum globulin and IgA levels. In conclusion, AAV patients with IgA deposition had the basis of IgA nephropathy and may present lower systemic disease activity. But it differs from pauci-immune AAV or IgA nephropathy by the possible activation of the classic complement pathway.

Clinical and pathological features of patients with antineutrophil cytoplasmic antibody-associated vasculitides concomitant with IgG4-related disease.

AIM: The characteristics and the pathogenesis of the concomitant antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immunoglobulin G4-related disease (IgG4-RD) have not been elucidated. METHOD: We included 92 AAV patients with renal biopsy results. Among them, 10 patients met both AAV and IgG4-RD criteria (concomitant group). The IgG subclasses of myeloperoxidase (MPO)-ANCA in both serum and renal tissue were measured and complement activation components were detected in serum. RESULTS: Patients in the concomitant group had both elevated serum IgG4 levels and positive MPO-ANCA. They had higher levels of eosinophil counts, serum globulin, IgG, IgE and C-reactive protein than patients in the AAV alone group. All 10 patients had glomerulonephritis with crescents and seven patients also had segmental necrosis of the glomerular capillary wall. Most of them also presented with storiform fibrosis and lymphoplasmacytic infiltration in renal interstitium with IgG4 positive plasma cells more than 10/high-power field. Eight patients achieved remission with improved renal function, the other two patients were on maintenance dialysis. The IgG4 subclass of MPO-ANCA was higher in the concomitant group than that in AAV alone group. A merge of IgG4 and MPO immunofluorescence was observed in parts of the mesangium of concomitant AAV and IgG4-RD patients. For complement components, Bb and mannose-binding lectin were elevated in serum of concomitant AAV and IgG4-RD patients. CONCLUSION: We showed a new overlap syndrome of AAV and IgG4-RD, in which the IgG4 subclass of ANCA may be a pathogenic factor.

The impact of intravenous methylprednisolone pulses on renal survival in anti-neutrophil cytoplasmic antibody associated vasculitis with severe renal injury patients: a retrospective study.

BACKGROUND: High-dose methylprednisolone pulses were one of the main treatments for anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitides (AAV) but had obvious side effects. We aimed to know the impact on renal survival and identify the prognostic factors of this treatment in Chinese AAV patients with severe renal involvement. METHODS: One hundred and eleven AAV patients with an estimated glomerular filtration rate (eGFR) of 10ml/min/1.73 m2 or less at admission were included. The MP group (n = 57) received intravenous methylprednisolone 500 mg/d for 3 days, while the control group (n = 54) had not. The outcomes and adverse events between two groups were compared. Besides, predictors for dialysis independence and good response of intravenous methylprednisolone were analyzed using Cox regression analysis and ROC curves respectively. RESULTS: Their median duration of follow-up was 31 (range 3 to 134) months. Eleven patients in MP group and 20 patients in control group were died (P = 0.056). Twenty-one patients (36.8%) in MP group and 29 patients (53.7%) in control group were on maintaining dialysis (P = 0.088). Twenty-one patients in MP group remained dialysis independent, more than those in control group (4 patients, P <0.01). Urine protein creatinine ratio (hazard ratio 1.730, 95% confidence interval 1.029 to 2.909, P = 0.039) and the treatment of intravenous methylprednisolone pulses (hazard ratio 0.362, 95% confidence interval 0.190 to 0.690, P = 0.002) were the independent risk factors for dialysis independence. Those patients with serum creatinine≥855µmol/L and urine protein ≥3.7g/24h at admission may have worse responses to intravenous methylprednisolone pulses (sensibility 56.7%, specificity 85.0%, PPV 100.0% and NPV57.1%). CONCLUSIONS: Intravenous methylprednisolone pulses could improve the long-term outcome in term of dialysis independence and tend to decrease mortality for Chinese AAV patients with severe renal involvement.

Tranexamic acid decreases blood loss in shoulder arthroplasty: A meta-analysis.

BACKGROUND: The objective of this meta-analysis was to evaluate the efficacy and safety of tranexamic acid (TXA) in shoulder arthroplasty (SA). METHODS: Academic articles were identified from the Cochrane Library, Medline (1966-2017.2), PubMed (1966-2017.2), Embase (1980-2017.2), and ScienceDirect (1966-2017.2). Randomized controlled trials (RCTs) and non-RCTs studying TXA in SA were included. Two independent reviewers conducted independent data abstraction. The I statistic was used to assess heterogeneity. Fixed- or random-effects models were used for meta-analysis. RESULTS: Two RCTs and 2 non-RCTs met the inclusion criteria. This meta-analysis found significant differences in postoperative hemoglobin reduction (MD = -0.71 g/dL), drainage volume (MD = -133.21 mL), and total blood loss (MD = -226.82 mL) between TXA groups and controls. There were no significant differences in blood transfusion requirements, operation time, or length of hospital stay. CONCLUSIONS: The use of TXA in SA decreases postoperative hemoglobin reduction, drainage volume, and total blood loss and does not increase the risk of complications. Because of the limited high-quality evidence currently available, additional randomized controlled trials are required.

Comparison of minimally invasive plate osteosynthesis and conventional plate osteosynthesis for humeral shaft fracture: A meta-analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy and safety of minimally invasive plate osteosynthesis (MIPO) and conventional plate osteosynthesis (CPO) for humeral shaft fracture. METHODS: Potential academic articles were identified from the Cochrane Library, Medline (1966-2016.3), PubMed (1966-2016.3), Embase (1980-2016.3), and ScienceDirect (1966-2016.3). Gray studies were identified from the references of the included literature. Randomized controlled trials (RCTs) and non-RCT involving MIPO and CPO for humeral shaft fracture were included. Two independent reviewers performed independent data abstraction. I statistic was used to assess heterogeneity. Fixed or random effects model was used for meta-analysis. RESULTS: Two RCTs and 3 non-RCTs met the inclusion criteria. There was a lower incidence of iatrogenic radial nerve palsy in patients with MIPO (P = 0.006). There was no statistically significant difference in in the risk of developing nonunion, delay union, malformation, screw loosening, infection, operation time, UCLA, and MEPS function score between the 2 groups. CONCLUSION: MIPO decreased incidence of iatrogenic radial nerve palsy and is an efficacy and safety technique for humeral shaft fracture. Due to the limited quality and data of the evidence currently available, more high-quality RCTs are required.

Cross-linked versus conventional polyethylene for total knee arthroplasty: a meta-analysis.

BACKGROUND: Highly cross-linked polyethylene (HXLPE) has been reported as an effective material for decreasing polyethylene wear and osteolysis in total knee arthroplasty (TKA). Because no single study to date has been large enough to definitively determine the benefit of HXLPE in TKA, we conducted a meta-analysis to pool the results from randomized controlled trials (RCTs) and non-RCTs to make such a determination. METHODS: Potential candidate articles were identified by searching the Cochrane Library, Medline (1966-2015.10), PubMed (1966-2015.10), Embase (1980-2015.10), ScienceDirect (1985-2015.10), and other databases. "Gray studies" were identified from the included articles' reference lists. Pooled data were analyzed using RevMan 5.1. RESULTS: Three RCTs and three non-RCTs were included in the meta-analysis. There were no significant differences between the groups in the total number of reoperations (P = 0.11), reoperations for prosthesis loosening (P = 0.08), radiolucent line (P = 0.20), osteolysis (P = 0.38), prosthesis loosening (P = 0.10), and mechanical failures related to the tibial polyethylene (P = 1.00). Similarly, no significant differences between the two groups were found in postoperative total knee score (P = 0.18) or functional score (P = 0.23). CONCLUSIONS: The meta-analysis showed that compared with conventional polyethylene, HXLPE did not improve the clinical and radiographic outcomes in mid-term follow-up after TKA. Additional high-quality multicenter prospective RCTs with good design, large study populations and long-term follow-up will be necessary to further clarify the effect of HXLPE in TKA.

[Treatment of tibiofibular syndesmosis together with ankle fracture using cortical screw].

OBJECTIVE: To investigate the clinical experiment of cortical screw in the treatment of tibiofibular syndesmosis separation together with ankle fractures. METHODS: From March 2008 to May 2012,42 patients with tibiofibular syndesmosis separation were treated with cortical screw, including 20 cases in the left and 24 cases in the right. All the patients had closed injury. According to Lauge-Hansen classification, there were 18 cases of supination-external rotation, in which 4 patients with injuries belong to type II, 8 patients with injuries belong to type III, 6 patients with injuries belong to type IV; 14 cases of pronation-external rotation, in which 6 patients with injuries belong to type III, 8 patients with injuries belong to type IV; and 12 cases of pronation-abduction, in which 4 patients with injuries belong to type II, 8 patients with injuries belong to type III. According to injury of ankle, 4 patients had injuries in one ankle, 28 patients had injuries in 2 ankles, and 12 patients had injuries in 3 ankles. All the patients were diagnosised definitely in sight of medical history, checking-up, iconography. The clinical effects were evaluated based on Baird-Jackson score and activity degree of ankle. RESULTS: All the patient were followed up, and the duration ranged from 11 to 23 months, with an average of 15.7 months. No postoperative wound infection, nonunion, and tibiofibular syndesmosis separation again and other complications occurred. Postoperative Baird-Jackson score exhibited 91.56 ± 6.26 (75 to 99), and 26 patients got an excellent result, 10 good, 6 poor and 2 bad. One patient had nail broken after operation,and got good function after removing broken nail without external fixation. Other 1 patient had osteoarthritis to 1 degree, and got better result with the treatment of physical therapy and intra-articular injection. CONCLUSION: Cortex screw is the effective treatment for tibiofibular syndesmosis separation. Clear diagnosis, delicate operation and postoperative reasonable functional exercise are primary factor of prognosis.

The biomechanical effects of osteoporosis vertebral augmentation with cancellous bone granules or bone cement on treated and adjacent non-treated vertebral bodies: a finite element evaluation.

BACKGROUND: In order to reduce the complications of bone cement, many efforts are underway to replace bone cement augmentation with cancellous bone granule augmentation for treating compression fractures of osteoporotic vertebral bodies. The goal of this study was to investigate the biomechanical effects of cancellous bone granule augmentation of Optimesh and polymethylmethacrylate augmentation of kyphoplasty on treated and adjacent non-treated vertebral bodies. METHODS: Three-dimensional, anatomically detailed finite element models of the L1-L2 functional spinal unit were developed on the basis of cadaver computed tomography scans. The material properties and plug forms of the L2 centrum were adapted to simulate osteoporosis, cancellous bone granule and polymethylmethacrylate augmentation. The models assumed a three-column loading configuration as the following types: compression, flexion and extension. FINDINGS: Compared with the osteoporotic model, changes in stress and strain at adjacent levels both of cancellous bone granule and polymethylmethacrylate augmentation models were minimal, but stresses/strains within the two reinforcement material plugs were modified distinctly and differently. In addition, osteoporosis and augmentation had little effect on either the axial compressive displacement of the three columns or the average disc internal pressure in all models. INTERPRETATION: Both cancellous bone granule and polymethylmethacrylate augmentation restore the total strength and stiffness level of treated vertebral bodies and benefit the reconstruction of vertebral function. Regarding the material mechanical compatibility and the biocompatibility of the treated vertebral body and reinforcement material, however, the morcelized cancellous bone is better than polymethylmethacrylate augmentation.

[Comparison of accuracy of pedicle screw placement in the thoracic spine using funnel technique and free hand technique].

OBJECTIVE: To study the accuracy the pedicle screw placement in the thoracic spine using funnel technique and free hand technique. METHODS: Eight cadavers including 5 males and 3 females were analysed. The age ranged from 57 to 82 years (mean 68 years). Cadawers were randomly assigned to one of two instrumentation groups. In four cadavers, "funnel technique" was used for screw placement. In the remaining four cadavers,free hand technique then was used. Success of pedicle screw placement was judged by CT scan. The rate of success of two ways was compared using statistic analysis. RESULTS: Ninety-six screws were inserted by "funnel technique" and free hand technique respectively, 84 of "funnel technique" were successful, and 73 of free hand technique were successful. Significant differences were found between two ways (P < 0.05). Chanciness tresis occurred in "funnel technique" on 2 screws and free hand technique on 9 screws. There were significant differences in rates of chanciness tresis (P < 0.05). CONCLUSION: Funnel technique is simple, safe and cost-effective alternative to any other thchnique for pedicle screw placement in thoracic spine,funnel technique is able to reduce the chance of critical injury of nerve root and dura.