A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway.

BACKGROUND Rotator cuff injury is the most common cause of shoulder disability, and although the repair technique has improved, the rate of rotator cuff reduction after repair is still high. The fibrocartilage region, which appears to be histologically inserted, cannot be regenerated. In recent years, studies have reported that mesenchymal stem cells (MSCs) have enhanced cartilage regeneration in the tendon and bone interface after rotator cuff repair, which has become a hot topic of research. MATERIAL AND METHODS Two mesenchymal stem cell types, SMSC (synovial-derived mesenchymal stem cells) and BMSC (bone marrow-derived mesenchymal stem cells) were intervened using kartogenin (KGN). The cytotoxicity was evaluated and the proliferation of the 2 cells was observed. Four commonly used cartilage phenotype genes were detected by quantitative real-time polymerase chain reaction, and the cartilage differentiation of MSCs induced by KGN was explored. The bidirectional regulation of the expression of BMP-7 and the downstream gene Smad5 was observed by constructing a lentiviral overexpression vector containing the target gene BMP-7. To explore whether BMP-7/Smad5 pathway activation promotes differentiation of SMSCs into chondrocytes. RESULTS KGN can induce the selective differentiation of endogenous MSCs into chondrocytes by activating the BMP-7/Smad5 pathway, which promotes the regeneration of interfacial cartilage, and improves the quality of tendon healing of the tendon after rotator cuff repair. CONCLUSIONS This study found a new biological intervention method to promote the effect of tendon on bone healing after rotator cuff repair.

Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion.

Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

Increased hepatic progenitor cell response and ductular reaction in patients with severe recurrent HCV post-liver transplantation.

OBJECTIVES: Post-liver transplant (LT) hepatitis C virus (HCV) patients may develop allograft cirrhosis and rarely fibrosing cholestatic hepatitis (FCH), while others have a stable course. Hepatic progenitor cells (HPC) may be implicated in liver injury and fibrogenesis through ductular reaction (DR). We studied HPC response and DR in three distinct post-LT patterns of HCV: stable recurrence, allograft cirrhosis, and FCH. METHODS: We identified 52 patients with untreated recurrent HCV and longitudinal liver biopsies (20 stable/23 cirrhosis/9 FCH) and eight healthy controls. Archived liver biopsy specimens for three time points (LT; initial recurrence; and clinical outcome) were stained for cytokeratin-7. Manual HPC counts and DR quantification using image analysis were performed. RESULTS: HCV counts and DR at LT did not differ across groups. At initial recurrence, HPC expansion occurred only in patients who developed cirrhosis, while prominent DR was present in those who developed FCH vs. stable and controls (p < 0.05). At outcome biopsies, HPC response and DR were increased in cirrhosis and FCH vs. stable and controls (p < 0.05). HPC response and DR did not differ in stable vs. CONCLUSIONS: These findings suggest that an altered HPC response assessed by cytokeratin-7 stain after LT may predict severity of HCV recurrence.

[Effect of anxin granules combined with tirofiba on patients with acute myocardial infarction after elective percutaneous coronary intervention].

To investigate the influence of Anxin granules combined with tirofiban on acute myocardial infarction (AMI) Patients after elective percutaneous coronary intervention (PCI). One hundred and twenty AMI patients were randomly divided into treatment group and control group. The patients in the two groups were all given Tirofiban 30mins before PCI . The treatment group was added Anxin granules 30 mins before and after PCI. Tissue factor (TF) and von willebrand factor (vWF) were tested at 6 hours after operation. Syndromatology alteration of traditional Chinese medicine (TCM) and bleeding complications were observed at 4 weeks after operation. Both TF and vWF at 6 hours after operation of the treatment group was lower than the control group significantly (P < 0.01), while the condition of myocardial ischemia at 90 mins after operation of the treatment group was better than control group with significance. The syndromatology alteration of TCM especially spontaneous perspiration and hypodynamia of the treatment group were improved significantly compared to control group 4 weeks after operation. All patients in both groups had no bleeding complications and thrombopenia. The study suggests that Anxin granules combined with tirofiba can improve the clinical efficacy and the endothelial function of AMI patients after PCI with no increase in bleeding events.

[Effect of extended release of posterior clearance on flexion clearence and range of motion of the knee in total knee arthroplasty].

OBJECTIVE: To observe the change of clearance and range of joint improved situation during total knee arthroplasty (TKA) by operating extended release manipulation of the posterior knee clearance. METHODS: A total of 120 patients with knee osteoarthritis undergoing unilateral TKA from March 2010 to March 2012 were equally randomized prospectively assigned to the experimental group and control group, each 60 cases. There were 46 male and 74 female patients, the mean age was 63.6 years (range from 49 to 75 years). After the osteotomy of the tibia and the femoral condyle and before the release of soft tissue intraoperation, patients in experimental group were taken the extended release manipulation of the posterior knee clearence while the control group were cleaned the osteophyte of the posterior condyle only, 2-sided paired t test was used to compare the clearence intraoperation and the time to flexion angle of 90° and 120° and the maximum angle after 3 months' follow-up. RESULTS: There was no significant difference of the index between the experimental group and control group (P > 0.05). Between experimental group and control group, the difference was significant in extention clearance ((18.9 ± 1.5) mm vs. (17.9 ± 1.6) mm, t = 3.53, P < 0.01) intraoperation, and no significant difference in flexion clearance ((20.7 ± 1.8) mm vs. (20.2 ± 1.9) mm, t = 1.48, P > 0.05). It took longer time for the knee flexion range of motion to 90°(t = 10.2399, P < 0.01) or 120°(t = 11.142, P < 0.01) of the control group than that of the experimental group, and the difference of the maximum range of motion between experimental group and control group was significant statistically at the 3-months follow-up (t = 4.4255, P < 0.01). All the patients were followed up for 3 - 24 months, average of 14.6 months, no femoral component loosening happened. CONCLUSIONS: Extended release of the posterior knee clearance benefits the knee extension clearence intraoperation and functional exercise of range of motion postoperation, while it is no meaning to the flexion clearence.

Automated 3D trajectory measuring of large numbers of moving particles.

Complex dynamics of natural particle systems, such as insect swarms, bird flocks, fish schools, has attracted great attention of scientists for years. Measuring 3D trajectory of each individual in a group is vital for quantitative study of their dynamic properties, yet such empirical data is rare mainly due to the challenges of maintaining the identities of large numbers of individuals with similar visual features and frequent occlusions. We here present an automatic and efficient algorithm to track 3D motion trajectories of large numbers of moving particles using two video cameras. Our method solves this problem by formulating it as three linear assignment problems (LAP). For each video sequence, the first LAP obtains 2D tracks of moving targets and is able to maintain target identities in the presence of occlusions; the second one matches the visually similar targets across two views via a novel technique named maximum epipolar co-motion length (MECL), which is not only able to effectively reduce matching ambiguity but also further diminish the influence of frequent occlusions; the last one links 3D track segments into complete trajectories via computing a globally optimal assignment based on temporal and kinematic cues. Experiment results on simulated particle swarms with various particle densities validated the accuracy and robustness of the proposed method. As real-world case, our method successfully acquired 3D flight paths of fruit fly (Drosophila melanogaster) group comprising hundreds of freely flying individuals.

The NF-κB pathway mediates lysophosphatidic acid (LPA)-induced VEGF signaling and cell invasion in epithelial ovarian cancer (EOC).

OBJECTIVES: Our previous report has implicated the involvement of VEGF-VEGFR-2 h signaling in LPA-induced EOC invasion. However, the mechanism by which LPA regulates VEGF and VEGFR-2 expression remains to be elucidated. In the present study, we systematically examined the signal transduction pathways activated by LPA and further evaluated whether LPA's effect on VEGF-VEGFR-2 signaling and EOC invasion was mediated by the activation of NF-κB pathway. METHODS: Using a signal transduction PathwayFinder PCR array, we examined the expression change of 86 key genes representing 18 signal transduction pathways in DOV13 and SKOV3 cells upon LPA (20 µM) treatment. We also used quantitative PCR, Western blotting and ELISA to evaluate the effect of NF-κB pathway inhibition on VEGF(121), VEGF(165) and VEGFR-2 mRNA and protein expression/secretion with or without the presence of LPA (20 µM) in SKOV3. Cell invasion under various treatment conditions was assessed by Matrigel invasion assay and MMP-2 secretion was detected by gelatin zymography. RESULTS: Our results showed that in both DOV13 and SKOV3, several of the NF-κB pathway components, such as TNF, are consistently activated by LPA stimulation. In addition, treatment with an NF-κB pathway activation inhibitor, at 10 µM, significantly decreased LPA-induced VEGF(121), VEGF(165) and VEGFR-2 mRNA expression and VEGF secretion, as well as LPA-induced SKOV3 invasion (p<0.05). When combined with an EGFR inhibitor, NF-κB pathway inhibition exhibited a significantly stronger effect than used alone (p<0.05) on reducing LPA-induced VEGF secretion and cell invasion. Additionally, NF-κB inhibition also decreased LPA-induced MMP-2 secretion and MMP-1 expression (p<0.05). CONCLUSIONS: These results suggest that the NF-κB pathway plays an important role in LPA-induced VEGF signaling and EOC invasion and targeting this pathway may reveal potential therapeutic options for metastatic EOC.

Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis.

Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.

Segmentation and thickness measurement of glomerular basement membranes from electron microscopy images.

An algorithm for segmentation and thickness measurement of the glomerular basement membranes (GBM) in electron microscopy kidney images is presented. Differences in intensities and variations between GBM and other components in the image are employed. Regions of extreme intensities such as the black area of blood cells and white areas of urinary spaces are pre-excluded. Areas of sharp edges are either at the GBM borders or unrelated to GBM regions. These non-GBM sharp edges, along with the pre-excluded regions, are used as barriers limiting the size of the fitting circles centered at a location in the image domain to form a two-dimensional function, proportional to the radius of the largest fitting circle, at the location. A local peak in the radius function corresponds to the largest circle in the local area. The set of the combined peaks in two perpendicular directions is calculated before a thinning procedure is applied. After removing the unwanted branches, a centerline of the GBM is produced. The segmentation of the GBM is then straightforward from expanding each point in the centerline to a circle of radius defined by the radius function. The average of the diameters of the circles gives the average GBM thickness. Results of the real GBM images are provided. Visual comparisons from the superimposed GBM boundaries show that the algorithm provides accurate GBM segmentation. The evaluations of the average GBM thicknesses are also compared to those from the manual tracing method.

Perinatal exposure to di-(2-ethylhexyl) phthalate leads to restricted growth and delayed lung maturation in newborn rats.

BACKGROUND: Pregnant women and infants have significant exposures to the most commonly used plasticizer di-(2-ethylhexyl) phthalate (DEHP). OBJECTIVES: This study was designed to evaluate the effects of DEHP exposure on growth and lung maturation in rats and determine if DEHP regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene (Hsd11b1) expression in the lung tissue plays a role in its effects on lung maturation. METHOD: Pregnant Sprague-Dawley rats were treated from gestational day 12 to postnatal day (PND) 21 with DEHP orally at dosages of 0, 10, 100 or 750 mg/kg/day, respectively (n=8 for each group). Two rat pups (one male and one female) from each litter were sacrificed at PND 1 and 21. Body weight was measured and the lung was processed for histology and calculation of lung interstitial tissue proportion as well as real-time PCR determination of the expressions of Hsd11b1, surfactant associated protein-A1 gene (Sftpa1) and B gene (Sftpb). RESULTS: The perinatal DEHP exposure led to a dose dependent intrauterine and postnatal growth restriction (P<0.001). High dose DEHP (750 mg/kg/day) exposure led to decreased gas-exchange space as evidenced by increased lung interstitial tissue proportion (P<0.001), but did not cause significant changes in Hsd11b1, Sftpa1 or Sftpb gene expression in the rat lung at PND 1. The DEHP-induced change in lung histology remained significant at PND 21 with improvement despite continual exposure to DEHP. CONCLUSION: Perinatal DEHP exposure leads to growth restriction and delayed lung maturation in newborn rats.

[The use of uncemented extensively porous-coated femoral components in the management of Vancouver type B2 periprosthetic femoral fractures].

OBJECTIVE: To assess the outcome of patients with Vancouver type B2 periprosthetic fractures treated with femoral revision using an uncemented extensively porous-coated implant. METHODS: From October 2002 to May 2007, a retrospective clinical and radiographic assessment of 10 patients with Vancouver type B2 periprosthetic fractures treated with femoral revision was evaluated, among which 4 was cement fixation, 6 was non-cement fixation in the index procedure. RESULTS: The mean follow-up for these patients was 44 months (range, 12 to 67 months). The mean Harris hip score was 87.6 points. All 10 reconstructions showed solid fracture union and a stable prosthesis, 8 was bone ingrowth, 2 was fibrous ingrowth. Complications in 4 patients included thigh pain in 1, stress shield in 3. CONCLUSIONS: Vancouver type B2 periprosthetic fractures treated with uncemented extensively porous-coated femoral stems incorporate distally allowing stable fixation.

ABCB1 Gene Is Associated With Clinical Response to SNRIs in a Local Chinese Han Population.

Background: The relation between the ATP-binding cassette subfamily B member 1 (ABCB1) gene and major depressive disorder (MDD) has been studied in a local Chinese Han population. MDD is associated with the rs2032582 (G2677T) and rs1128503 (C1236T) single-nucleotide polymorphisms (SNPs) of ABCB1 but not with rs1045642, rs2032583, rs2235040, and rs2235015. This study aims to explore the potential correlations of therapeutic responses with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a local Chinese Han population. Methods: The study population included 292 patients with MDD. All patients were assessed at baseline and at first, second, fourth, and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAM-D17) to determine their therapeutic responses to SSRIs and SNRIs. Results: In the SSRI therapy group, the genotype or allele distribution of six SNPs was not significantly different between responders and nonresponders. In the SNRI therapy group, only rs2032583 was associated with a therapeutic response to SNRIs. The C allele of the ABCB1 rs2032583 polymorphism was negatively correlated with therapeutic responses according to logistic regression analysis. Conclusion: The ABCB1 gene polymorphisms may not be associated with therapeutic responses to SSRIs but not with SNRIs. The TT genotype of rs2032583 could be a predictive factor of improved treatment responses to SNRIs in the Chinese population. These findings should be replicated in future studies with larger patient groups.

Regression of hepatic fibrosis after intestinal transplantation in total parenteral nutrition liver disease.

BACKGROUND & AIMS: Hepatic fibrosis may occur in patients with intestinal failure requiring total parenteral nutrition, leading to liver dysfunction necessitating combined intestinal and liver transplantation. The decision to perform combined transplantation as opposed to an isolated intestinal transplant is based on the presence of hyperbilirubinemia, portal hypertension, and advanced hepatic fibrosis. METHODS: We identified 4 patients who underwent isolated intestinal transplantation having significant liver fibrosis. A novel image analysis technique was applied to serial liver biopsies to more precisely quantitate posttransplantation fibrosis regression separately within both portal and centrilobular areas. RESULTS: All patients were found to have significant portal and centrilobular fibrosis regression, which occurred more rapidly in the former. Two patients had improvement in fibrosis despite infections and continuation of total parenteral nutrition, suggesting that hepatic fibrosis associated with intestinal failure may in part be related to adequate anatomic and functional bowel length. CONCLUSIONS: Significant hepatic fibrosis and liver dysfunction may regress after intestinal transplantation and fibrosis regresses more rapidly in portal areas. This suggests that some patients with intestinal failure and associated liver disease may safely undergo isolated intestinal transplant without the need for concurrent liver transplantation and its attendant higher morbidity and mortality.

Segmentation of Brain Immunohistochemistry Images Using Clustering of Linear Centroids and Regional Shapes.

A generalized clustering algorithm utilizing the geometrical shapes of clusters for segmentation of colored brain immunohistological images is presented. To simplify the computation, the dimension of vectors composed from the pixel RGB components is reduced from three to two by applying a de-correlation mapping with the orthogonal bases of the eigenvectors of the auto-covariance matrix. Since the brain immunohistochemical images have stretched clusters that appear long and narrow in geometrical shape, we use centroids of straight lines instead of single points to approximate the clusters. An iterative algorithm is developed to optimize the linear centroids by minimizing the approximation mean-squared error. The partitioning of the two-dimensional vector domain into three portions classifies each image pixel into one of the three classes: The microglial cell cytoplasm, the combined hematoxylin stained cell nuclei and the neuropil, and the pale background. Regions of the combined hematoxylin stained cell nuclei and the neuropil are to be separated based on the differences in their regional shapes. The segmentation results of real immunohistochemical images of brain microglia are provided and discussed.

[The use of a pneumatic tourniquet in total knee arthroplasty: a prospective, randomized study].

OBJECTIVE: To determine the value of the use of a pneumatic tourniquet in total knee arthroplasty. METHODS: Sixty patients were prospectively randomized into 2 groups, one group underwent total knee replacement with a tourniquet (n = 30) and one without (n = 30). Operating time, blood loss, postoperative mean morphine requirement, swelling, ecchymosis, earlier straight-leg raising and postoperative knee flexion were measured in both groups. RESULTS: There was no significant difference in the total blood loss between the 2 groups although the intraoperative blood loss was significantly greater in those without a tourniquet. The mean morphine requirement, postoperative swelling, scope of ecchymosis, earlier straight-leg raising and postoperative knee flexion in the patients that had surgery without a tourniquet were significantly better than those with a tourniquet. CONCLUSION: Knee arthroplasty operation with the use of a tourniquet has only small benefits on the total blood loss, but hinder in patients' early postoperative rehabilitation exercises.

[Effect of total hip replacement on lumbago in unilateral developmental hip dysplasia].

OBJECTIVE: To assess the effect of total hip replacement on lumbago in patients with unilaterally developmental hip dysplasia. METHODS: From January 2001 to January 2006, 39 adult patients with unilateral developmental hip dysplasia co-exiting lumbago were included. Among them, there were 32 females and 7 males, age from 38 years to 73 years. According to Crowe classification system, there were 4 in type I, 20 in type II,8 in type III and 7 in type IV. They were performed total hip replacement. The Harris Hip Score and the Oswestry Disability Index were used to evaluate hip and spine symptoms in same patient before and 3, 24 months after operation. RESULTS: Thirty-nine patients were evaluated, both hip and spinal pain and function were significant improved. The mean Harris score increased from 44 to 84 (P < 0.01). The mean Oswestry Scores dropped from 36 to 25 (P < 0.01). CONCLUSION: Spinal function and lumbago is improved after total hip replacement in patients with unilateral developmental hip dysplasia at 3 months, which is maintained and enhanced in 2 years.

[Patella reshaping versus resurfacing in total knee arthroplasty: a prospective randomized study].

OBJECTIVE: To investigate the differences in the clinical outcome of total knee arthroplasty according to patellar reshaping or resurfacing. METHODS: From January 2002 to December 2002, 60 patients (60 knees) undergoing primary total knee arthroplasty for the treatment of osteoarthritis were enrolled in a prospective, randomized study. All patients received the same posterior-cruciate-substituting total knee prosthetic components. Patients were randomized to the treatment with reshaping or resurfacing of the patella, and the results were followed up for a mean of 54 months (40-60 months). Evaluations consisted of the determination of a Knee Society Score, range of motion for knees, patient satisfaction, and radiographs. RESULTS: With the numbers available for study, no significant difference was found between the knees that had patellar resurfacing and those that had patellar reshaping with regard to the overall score (P=0.12), the subscore for pain (P=0.90), and patient satisfaction (P=0.22). The results showed that the same prevalence of any anterior knee pain in two groups was 10%, and it did not represent a significant difference. The two groups showed statistical difference with regard to the total function score and range of motion. CONCLUSIONS: It has shown that total knee arthroplasty with patella reshaping or resurfacing dramatically relieves pain and improves the function. It seems that postoperative anterior knee pain is related either to the component design or to the details of the surgical technique, rather than to whether or not the patella is resurfaced.

A biased median filtering algorithm for segmentation of intestinal cell gland images.

In this paper, we introduce a biased median filtering image segmentation algorithm for intestinal cell glands consisting of goblet cells. While segmentation of individual cells are generally based on the dissimilarities in intensities, textures, and shapes between cell regions and background, the proposed segmentation algorithm of intestine cell glands is based on the differences in cell distributions. The intestine cell glands consist of goblet cells that are distributed in the chain-organized patterns in contrast to the more randomly distributed nongoblet cells scattered in the bright background. Four biased median filters with long rectangular windows of identical dimension, but different orientations, are designed based on the shapes and distributions of cells. Each biased median filter identifies a part of gland segments in a particular direction. The complete gland regions are the combined responses of the four biased median filters. A postprocessing procedure is designed to reduce the defects that may occur when glands are located very close together and to narrow the gapping areas because of the thin distribution of goblet cells. Segmentation results of real intestinal cell gland images are provided to show the effectiveness of the proposed algorithm.

[Radiographic analysis of rotational malalignment between tibial component and femoral component in total knee arthroplasty].

OBJECTIVE: To identify possible reasons of rotational mismatch between tibial component and femoral component in total knee arthroplasty and choose a right reference axis for placing the components in the operation and to decrease the complications. METHODS: Forty normal Chinese knees were studied. There were 20 men and 20 women, and average age was 34 years (range, 18 - 42 years). The images of cross sections of the distal femur were obtained by spiral CT scanning (0.5 mm thickness). Scan direction was aligned to be in the plane perpendicular to the mechanical axis of the tibia. On the images of the distal femur and the proximal tibia, three baselines for the anteroposterior axis of the femoral component were drawn based on the clinical epicondylar axis and the surgical epicondylar axis and 3 degrees lateral rotated to the posterior condylar surfaces of the femur separately, and a baseline for the anteroposterior axis of the tibial component was drawn based on the medial 1/3 of the tibial tuberosity. The rotational mismatch angles were measured between each component by using the Autocad software. RESULTS: The mean rotational mismatch angle between tibial component and femoral component is 2.94 degrees for the clinical epicondylar axis, 6.50 degrees for the surgical epicondylar axis and 6.83 degrees for 3 degrees lateral rotation of the femoral component referenced to the posterior condylar axis separately. CONCLUSIONS: Landmarks of each bone were the intrinsic cause of the rotational mismatch in total knee arthroplasty. The clinical epicondylar axis can be chosen for the ideal reference to rotational alignment of the femoral component because of its minimal rotational mismatch between each component.