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.

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.

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.

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.

[Case-control study on midterm follow-up effects of the extended release of posterior clearance in total knee arthroplasty].

OBJECTIVE: To evaluate the midterm follow-up results of extended release of posterior clearance in total knee arthroplasty. METHODS: A total of 120 patients with knee osteoarthritis were equally randomly assigned to the experimental group and control group, and underwent unilateral TKA from March 2010 to March 2012. In experimental group, there were 21 males and 39 females with an average age of (62.2±10.9) years old. In the control group, there were 25 males and 35 females with an average age of (64.9±11.4) years old. All the patients were performed using the anterior knee approach. During operation, after osteotomy of the tibia and the femoral condyle, extended release of the posterior knee clearance were taken in experimental group, while only the clearance of osteophyte in the posterior condyle were performed in the control group. The KSS scores including knee functional score and knee clinical score,as well as the range of motion (ROM) of patients, were compared between the two groups at midterm follow-up. RESULTS: Totally 49 patients in the experimental group and 54 patients in the control group were followed up, and the median follow-up time was 46 months. The knee functional score of patients in the experimental group was 91.3±3.4, which was better than 86.4±3.9 of patients in the control group; initiative ROM of flexion of patients in the experimental group was (133.2±5.9)°, which was better than (126.9±7.4)° of patients in the control group. There were no significant difference of knee clinical score between 86.9±4.6 of patients in the experimental group and 85.7±5.1 of patients in the control group, and the initiative ROM of extension between (0.5±1.1)° and (0.3±1.2)°. CONCLUSION: Extended release of the posterior knee clearance contributes to the knee function and initiative flexion ROM during a midterm follow-up and patients benefit.

[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.

Visual sensory networks and effective information transfer in animal groups.

Social transmission of information is vital for many group-living animals, allowing coordination of motion and effective response to complex environments. Revealing the interaction networks underlying information flow within these groups is a central challenge. Previous work has modeled interactions between individuals based directly on their relative spatial positions: each individual is considered to interact with all neighbors within a fixed distance (metric range), a fixed number of nearest neighbors (topological range), a 'shell' of near neighbors (Voronoi range), or some combination (Figure 1A). However, conclusive evidence to support these assumptions is lacking. Here, we employ a novel approach that considers individual movement decisions to be based explicitly on the sensory information available to the organism. In other words, we consider that while spatial relations do inform interactions between individuals, they do so indirectly, through individuals' detection of sensory cues. We reconstruct computationally the visual field of each individual throughout experiments designed to investigate information propagation within fish schools (golden shiners, Notemigonus crysoleucas). Explicitly considering visual sensing allows us to more accurately predict the propagation of behavioral change in these groups during leadership events. Furthermore, we find that structural properties of visual interaction networks differ markedly from those of metric and topological counterparts, suggesting that previous assumptions may not appropriately reflect information flow in animal groups.

[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.

Patellar reshaping versus resurfacing in total knee arthroplasty - Results of a randomized prospective trial at a minimum of 7 years' follow-up.

OBJECTIVE: To compare the results of primary total knee arthroplasty with patellar reshaping or resurfacing. METHODS: One hundred thirty-three patients were randomized into patellar reshaping group and patellar resurfacing group. Patellar reshaping includes resecting the partial lateral facet of the patella and the osteophytes surrounding the patella, trimming the patella to match the trochlea of the femoral component. The minimum follow-up time was 7 years. The outcome was measured by anterior knee pain rate, Knee Society clinical score, and radiographs. RESULTS: Eight patients in the reshaping group (12.5%) and 10 patients in the resurfacing group (14.7%) complained of anterior knee pain (P=0.712). Meanwhile, there were no significant differences between the two groups in terms of total Knee Society score, Knee Society pain score, Knee Society function score, as well as anterior knee pain rate. CONCLUSIONS: With the numbers available, there was no significant difference between the groups treated with patellar reshaping or patellar resurfacing with regard to the KSS, anterior knee pain rate and radiographs. We prefer reshaping the patella to resurfacing the patella because the former preserves sufficient patellar bone stock and can easily be converted to patellar replacement if patients complain of recurrent anterior knee pain.

Recognition of linear stress fibers based on Hough transform.

OBJECTIVE: To present an algorithm based on Hough transform for recognition and extraction of linear stress fibers formed on exposure to lysophosphatidic acid (LPA). STUDY DESIGN: A ridge set of head points with lower shoulders is calculated, followed by a thinning process shrinking long, narrow regions to regions of single pixel thickness, then converted into a rectangular map whose value is the number of regional points in the path of a straight line at the angle and intercept determined by two coordinates. The location of the maximum in the map is sought, and the corresponding line with an unlimited length is constructed from the paired coordinates. We removed the line before repeating the process for the next longest straight line, continuing until all lines with reasonable lengths are extracted. RESULTS: Application of the algorithm to the stress fiber images of DOV13 cells stained with Texas red-phalloidin on LPA and AG1478 demonstrates close matches between stress fibers in the original images and linear lines. CONCLUSION: An algorithm for recognition of linear stress fibers formed on exposure to LPA is described and applications to stress fiber images using DOV13 cells with Texas red-phalloidin staining are demonstrated.

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.

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.

Co and Cr accumulation in hair after metal-on-metal hip resurfacing arthroplasty.

BACKGROUND: Currently, it is unclear whether Co and Cr levels are persistently elevated in the body after hip resurfacing arthroplasty (HRA). This study aimed to evaluate Co and Cr levels in the body after HRA using hair as samples. METHODS: Among 22 patients who had metal-on-metal HRA(m-o-m group) using the DePuy ASR system, scalp hair of 1.5 cm in length and 2 g in weight was collected before and at 6 and 12 months after surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to detect Co and Cr levels in the scalp hair. Another 22 patients with total hip replacements were randomly selected from a similar age range as controls (m-o-p group). Metal levels in hair were detected with multiple measurements and analysed by repeated measures analysis of variance. RESULTS: Both Co and Cr levels were significantly increased in the m-o-m group after surgery compared with those in the m-o-p group (P < 0.01). Co levels at 6 months post-operatively were 12-fold those before surgery, and Co levels 12 months postoperatively were lower than those at 6 months, but this difference was not significant (P = 0.0805) between the two time points in the m-o-m group. Cr levels were persistently elevated after surgery and were increased by 10-fold compared with those at baseline in the m-o-m group. CONCLUSIONS: Co and Cr levels in scalp hair are ideal indicators for metal levels in the body after HRA. Co and Cr levels in the body were greatly increased after metal-on-metal HRA. Long-term accumulation of these metals needs to be further investigated

[Short-term result of hip resurfacing arthroplasty in the treatment of patients with femoral head necrosis].

OBJECTIVE: To study short-term results of hip resurfacing arthroplasty (HRA) in the treatment of patients with avascular necrosis of femoral head (ANFH), and to explore indication and strategy in this surgery. METHODS: From December 2006 to December 2009, 37 patients (43 hips) with avascular necrosis of femoral head were treated with total hip resurfacing arthroplasty. Among the patients, 25 patients were male and 12 patients were female, with an average age of 44.5 years (ranged, 21 to 67 years). According to ARCO classification, 3 hips were 3A stage, 6 hips were 3B stage, 16 hips were 3C stage and 18 hips were 4 stage. X-ray evaluation of the patients were conducted. The clinical results were evaluated by the Harris hip score system including pain,range of motion, correction of deformity and total function. RESULTS: Thirty-four patients (40 hips) were followed up with an average period of 32.4 months (ranged, 16 to 53 months), and 3 patients were lost. Thirty-seven hips got complete relief of joint pain and 3 patients feel aching pain after walking. There was 1 heterotopic ossification, no femoral neck fracture no dislocation, no infection and no revision in all patients. From pre-operation to present, the average Harris hip score improved significantly from (51.5 +/- 1.7) to (94.3 +/- 1.4). Thirty-seven hips got an excellent result, 3 hips good and no poor. CONCLUSION: The total hip resurfacing arthroplasty is an effective solution for the problems of the younger and active patients with ANFH, and the short-term results are satisfying.

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.