Prediction of myelopathic level in cervical spondylotic myelopathy using diffusion tensor imaging.

PURPOSE: To investigate the use of a newly designed machine learning-based classifier in the automatic identification of myelopathic levels in cervical spondylotic myelopathy (CSM). MATERIALS AND METHODS: In all, 58 normal volunteers and 16 subjects with CSM were recruited for diffusion tensor imaging (DTI) acquisition. The eigenvalues were extracted as the selected features from DTI images. Three classifiers, naive Bayesian, support vector machine, and support tensor machine, and fractional anisotropy (FA) were employed to identify myelopathic levels. The results were compared with clinical level diagnosis results and accuracy, sensitivity, and specificity were calculated to evaluate the performance of the developed classifiers. RESULTS: The accuracy by support tensor machine was the highest (93.62%) among the three classifiers. The support tensor machine also showed excellent capacity to identify true positives (sensitivity: 84.62%) and true negatives (specificity: 97.06%). The accuracy by FA value was the lowest (76%) in all the methods. CONCLUSION: The classifiers-based method using eigenvalues had a better performance in identifying the levels of CSM than the diagnosis using FA values. The support tensor machine was the best among three classifiers.

Liver X receptor α inhibits osteosarcoma cell proliferation through up-regulation of FoxO1.

BACKGROUND: Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. METHODS: We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRα's potential role in regulating cell proliferation in Saos-2 and U2OS cells. RESULTS: We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region. CONCLUSION: LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.

3-D Brain Reconstruction by Hierarchical Shape-Perception Network From a Single Incomplete Image.

3-D shape reconstruction is essential in the navigation of minimally invasive and auto robot-guided surgeries whose operating environments are indirect and narrow, and there have been some works that focused on reconstructing the 3-D shape of the surgical organ through limited 2-D information available. However, the lack and incompleteness of such information caused by intraoperative emergencies (such as bleeding) and risk control conditions have not been considered. In this article, a novel hierarchical shape-perception network (HSPN) is proposed to reconstruct the 3-D point clouds (PCs) of specific brains from one single incomplete image with low latency. A branching predictor and several hierarchical attention pipelines are constructed to generate PCs that accurately describe the incomplete images and then complete these PCs with high quality. Meanwhile, attention gate blocks (AGBs) are designed to efficiently aggregate geometric local features of incomplete PCs transmitted by hierarchical attention pipelines and internal features of reconstructing PCs. With the proposed HSPN, 3-D shape perception and completion can be achieved spontaneously. Comprehensive results measured by Chamfer distance (CD) and PC-to-PC error demonstrate that the performance of the proposed HSPN outperforms other competitive methods in terms of qualitative displays, quantitative experiment, and classification evaluation.

Quantitative modeling of transcriptional regulatory networks by integrating multiple source of knowledge.

A key challenge in the post genome era is to identify genome-wide transcriptional regulatory networks, which specify the interactions between transcription factors and their target genes. In this work, a regulatory model-based binding energy is proposed to quantify the transcriptional regulatory network. Multiple quantities, including binding affinity, regulatory efficiency, and the activity level of transcription factor (TF) are incorporated into a general learning model. The sequence features of the promoter are exploited to derive the binding energy. Comparing with the previous models that only employ microarray data, the proposed model can bridge the gap between the relative background frequency of the observed nucleotide and the gene's transcription rate. Experimental results show that the proposed model can effectively identify the parameters and the activity level of TF. Moreover, the kinetic parameters introduced in the proposed model can reveal more biological sense than some previous models can do.

[Effects of rat serum containing Chinese herbal medicine Sangen Decoction on osteoclastogenesis and bone resorption of osteoclasts induced by polymethylmethacrylate particles].

OBJECTIVE: To investigate the effects of Sangen Decoction, a compound Chinese herbal medicine, on osteoclastogenesis and bone resorption function of osteoclasts induced by polymethylmethacrylate particles in vitro. METHODS: Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) were used to induce differentiation of bone marrow-derived macrophages (BMMs) towards osteoclasts. BMMs and polymethylmethacrylate particles with ratio of 1:3 were added to the 24-well plate and 96-well plate with bone slices respectively. A total of 50 male SD rats were divided into 5 groups randomly with each group containing 10 rats. After being treated with different drugs, serum samples of rats in each group were extracted, i.e., the blank serum, Western medicine (ibandronate) serum and high-, medium-, and low-dose Sangen Decoction serum and were added to the medium respectively. The tartrate-resistant acid phosphatase (TRAP) staining was used to identify the differentiation of BMMs and for counting of osteoclasts. Area of lacuna induced by osteoclast bone resorption on the bone slices was measured by computer image processing. RESULTS: Numbers of osteoclasts of treatment groups were less than that of blank group by TRAP staining (P<0.05); numbers of osteoclasts of positive control group and high-dose Sangen Decoction group were much lower than those of medium- and low-dose Sangen Decoction groups (P<0.05), and no difference was found between Western medicine group and high-dose Sangen Decoction group (P>0.05). In bone resorption assay, area of lacuna of blank group was larger than those of treatment groups (P<0.05); areas of lacuna of Western medicine group and high-dose Sangen Decoction group were much smaller than those of medium- and low-dose Sangen Decoction groups (P<0.05), and no difference was found between Western medicine group and high-dose Sangen Decoction group (P>0.05). CONCLUSION: Sangen Decoction can inhibit osteoclastogenesis induced by polymethylmethacrylate particles as well as bone resorption function of osteoclasts.

New Mutation of Coenzyme Q10 Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. METHODS: Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q10 monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX. RESULTS: Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. CONCLUSIONS: This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD. METHODS: Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining. RESULTS: In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs. CONCLUSIONS: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.

[Bridging fixation with locking plate for the treatment of subtrochanteric femoral fractures of Seinsheimer type V].

OBJECTIVE: To investigate the clinical effect of bridging fixation with locking plate for the Seinsheimer type V subtrochanteric femoral fracture. METHODS: From March 2009 to September 2014,18 cases of Seinsheimer type V subtrochanteric femoral fracture were treated by open reduction and bridging fixation with locking plate through proximal and distal approach including 16 males and 2 females with an average age of 41 years old ranging from 22 to 67 years old. Among them, 12 cases caused by traffic accident, 5 cases by falling, 1 case by heavy aboving. All cases were fresh and closed fractures. Time between injury and operation was from 4 to 9 days with an average of 6.2 days. Of them, 11 cases were fixed with reverse LISS and the other 7 cases were fixed with anatomical locking plates of proximal femur. RESULTS: The mean time of operation was 110 min (ranged from 90 to 155 min). The mean blood loss during operation was 425 ml (ranged from 350 to 650 ml) and 16 cases got blood transfusion which was meanly 300 ml. The mean hospital time was 14 days (ranged from 12 to 18 days). The mean duration of followed up was 11.8 months (ranged from 8 to 22 months). The mean time of bone union was 6.6 months (ranged from 5 to 8 months). There was not any complication such as infection, implant failure, hip varus, external rotation deformity of low limb or fat embolism. The Sanders hip scores were 53.22 ± 6.48, the result was excellent in 12 cases and good in 6 cases at the last follow-up. CONCLUSION: Under the principle of biological osteosynthesis, treatment of Seinsheimer type V subtrochanteric femoral fracture with bridging locking plate fixation has such advantages as high mechanism, less interference of blood supply, stable fixation and little complication. It is a safe and idea way for the treatment of the Seinsheimer type V subtrochanteric femoral fracture.

Hepatic actinomycosis: report of one case and analysis of 32 previously reported cases.

Hepatic actinomycosis is rare, with few published cases. There are no characteristic clinical manifestations, and computed tomography (CT) shows mainly low-density images, making clinical diagnosis difficult, and leading to frequent misdiagnosis as primary liver cancer, metastatic liver cancer or liver abscess. Diagnosis normally requires examination of both the aetiology and pathology. This article reports one male patient aged 55 who was hospitalized because of repeated upper abdominal pain for more than 2 mo. He exhibited no chills, fever or yellow staining of the skin and sclera, and examination revealed no positive signs. The routine blood results were: haemoglobin 110 g/L, normal numbers of leukocytes and neutral leukocytes, serum albumin 32 g/L, negative serum hepatitis B markers and hepatitis C antibodies, normal tumour markers (alpha-fetoprotein and carcinoembryonic antigen). An abdominal CT scan revealed an 11.2 cm × 5.8 cm × 7.4 cm mass with an unclear edge in the left liver lobe. The patient was diagnosed as having primary liver cancer, and left lobe resection was performed. The postoperative pathological examination found multifocal actinomycetes in the hepatic parenchyma, which was accompanied by chronic suppurative inflammation. A focal abscess had formed, and large doses of sodium penicillin were administered postoperatively as anti-infective therapy. This article also reviews 32 cases reported in the English literature, with the aim of determining the clinical features and treatment characteristics of this disease, and providing a reference for its diagnosis and treatment.

Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK pathway.

Galectin-1 (GAL1), a widely expressed ß­galacto-side-binding protein, exerts pleiotropic biological functions. GAL1 has been found to be upregulated in many malignancies; yet the role of GAL1 in the pathophysiology of human osteosarcoma (OS) remains uncertain. The present study was carried out to investigate the expression of GAL1 in human OS tissues and to explore its effects on the growth and invasion of OS cells. OS and corresponding adjacent non-cancerous tissues (ANCT) were collected from 30 consecutive cases. The expression of GAL1 was detected by immunohistochemical assay through tissue microarray procedure. Using small hairpin RNA (shRNA)-mediated GAL1 knockdown (Lv-shGAL1) in OS (MG-63 and U-2 OS) cells, we observed the changes in the malignant phenotype in OS cells in vitro and in vivo. As a consequence, the positive expression of GAL1 was significantly higher in OS tissues than that in the ANCT (63.3 vs. 36.7%, P=0.029), and was positively correlated with distant metastasis in the OS patients (P=0.022). Knockdown of GAL1 suppressed cell proliferative activities and invasive potential and induced apoptosis in OS cells with decreased expression of p38MAPK, p-ERK, Ki-67 and matrix metallopeptidase-9 (MMP-9) and increased expression of caspase-3. In addition, the tumor volume in the MG-63 subcutaneous tumor models treated with Lv-shGAL1 was significantly smaller than that in the negative control (NC) group (P<0.01). Altogether, our findings indicate that high expression of GAL1 is associated with distant metastasis of OS patients, and knockdown of GAL1 inhibits growth and invasion of OS cells possibly through inhibition of the MAPK/ERK pathway, suggesting that GAL1 may represent a potential target for the treatment of cancer.

Bayesian inference based modelling for gene transcriptional dynamics by integrating multiple source of knowledge.

BACKGROUND: A key challenge in the post genome era is to identify genome-wide transcriptional regulatory networks, which specify the interactions between transcription factors and their target genes. Numerous methods have been developed for reconstructing gene regulatory networks from expression data. However, most of them are based on coarse grained qualitative models, and cannot provide a quantitative view of regulatory systems. RESULTS: A binding affinity based regulatory model is proposed to quantify the transcriptional regulatory network. Multiple quantities, including binding affinity and the activity level of transcription factor (TF) are incorporated into a general learning model. The sequence features of the promoter and the possible occupancy of nucleosomes are exploited to estimate the binding probability of regulators. Comparing with the previous models that only employ microarray data, the proposed model can bridge the gap between the relative background frequency of the observed nucleotide and the gene's transcription rate. CONCLUSIONS: We testify the proposed approach on two real-world microarray datasets. Experimental results show that the proposed model can effectively identify the parameters and the activity level of TF. Moreover, the kinetic parameters introduced in the proposed model can reveal more biological sense than previous models can do.

Root features related to plant growth and nutrient removal of 35 wetland plants.

Morphological, structural, and eco-physiological features of roots, nutrient removal, and correlation between the indices were comparatively studied for 35 emergent wetland plants in small-scale wetlands for further investigation into the hypothesis of two types of wetland plant roots (Chen et al., 2004). Significant differences in root morphological, structural, and eco-physiological features were found among the 35 species. They were divided into two types: fibrous-root plants and thick-root plants. The fibrous-root plants had most or all roots of diameter (D) ≤ 1 mm. Roots of D > 1 mm also had many fine and long lateral roots of D ≤ 1 mm. The roots of these plants were long and had a thin epidermis and a low degree of lignification. The roots of the thick-root plants were almost all thicker than 1 mm, and generally had no further fine lateral roots. The roots were short, smooth, and fleshy, and had a thick epidermis. Root porosity of the fibrous-root plants was higher than that of the thick-root plants (p = 0.001). The aerenchyma of the fibrous-root plants was composed of large cavities which were formed from many small cavities, and distributed radially between the exodermis and vascular tissues. The aerenchyma of the thick-root plants had a large number of small cavities which were distributed in the mediopellis. The fibrous-root plants had a significantly larger root biomass of D ≤ 1 mm, of 1 mm < D < 3 mm, above-ground biomass, total biomass, and longer root system, but shorter root longevity than those of the thick-root plants (p = 0.003, 0.018, 0.020, 0.032, 0.042, 0.001). The fibrous-root plants also had significantly higher radial oxygen loss (ROL), root activity, photosynthetic rate, transpiration rate, and removal rates of total nitrogen and total phosphorus than the thick-root plants (p = 0.001, 0.008, 0.010, 0.004, 0.020, 0.002). The results indicate that significantly different root morphological and structural features existed among different wetland plants, and these features had a close relationship to nutrient removal capacity.