An interactive dose optimizer based on population pharmacokinetic study to guide dosing of methotrexate in Chinese patients with osteosarcoma.

PURPOSE: Osteosarcoma is a rare tumor with an incidence of 4.4 cases per million per year in adolescent. High-dose methotrexate (HD-MTX) is the standard first-line chemotherapeutic agent for osteosarcoma. However, its efficacy can vary significantly among individuals due to wide pharmacokinetic variability. Despite this, only a few population pharmacokinetics (popPK) models based on Chinese patients with osteosarcoma have been reported. Thus, this study aimed to develop a HD-MTX popPK model and an individual model-based dose optimizer for osteosarcoma therapy. METHOD: A total of 680 MTX serum concentrations from 57 patients with osteosarcoma were measured at the end of MTX infusion and 10 h, 24 h, 48 h, and 72 h after the start of infusion. Using the first-order conditional estimation method with NONMEM, a popPK model was estimated. Goodness-of-fit plots, visual predictive checks, and bootstrap analysis were generated to evaluate the final model. A dose optimizer tool was developed based on the validated models using R Shiny. Additionally, clinical data from 12 patients with newly diagnosed osteosarcoma were collected and used as the validation set to preliminarily verify the predictive ability of the popPK model and the dose optimizer tool. RESULTS: Body surface area (BSA) was the most significant covariate for compartment distribution. Creatinine clearance (CrCL) and co-administration of NSAIDs were introduced as predictors for central compartmental and peripheral compartmental clearance, respectively. Co-administration of NSAIDs was associated with significantly higher MTX concentrations at 72 h (p = 0.019). The dose optimizer tool exhibited a high consistency in predicting MTX AUC compared to the actual AUC (r = 0.821, p < 0.001) in the validation set. CONCLUSION: The dose optimizer tool could be used to estimate individual PK parameters, and optimize personalized MTX therapy in particular patients.

Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional mendelian-randomization study.

Background: The impact of inflammatory factors on the development of Ankylosing Spondylitis (AS) is widely recognized, but the exact causal relationship remains unclear. Methods: The bidirectional mendelian-randomization study utilized genetic data from a genome-wide association study (GWAS) of 186 AS cases and 456,162 controls of European ancestry. Inflammatory cytokines were obtained from a GWAS summary of 8,293 healthy participants. Causal associations were primarily investigated using the inverse variance-weighted method, supplemented by MR Egger, weighted median and weighted mode analyses. Heterogeneity in the results was assessed using the Cochrane Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers (MR-PRESSO) test. Sensitivity analysis was conducted through leave-one-out analysis. Results: The results suggest a genetically predicted potential association between beta-nerve growth factor (ßNGF), Interleukin-1-beta (IL-1ß), and TNF-related apoptosis inducing ligand (TRAIL) with the risk of AS (OR: 2.17, 95% CI: 1.13-4.16; OR: 0.41, 95% CI: 0.18-0.95,; OR: 1.47, 95% CI: 1.02-2.13).Additionally, Interleukin-12p70 (IL-12p70), Interleukin-17 (IL-17), Interleukin-6 (IL-6), Interleukin-4 (IL-4), Stromal-cell-derived factor 1 alpha (SDF-1α), Macrophage inflammatory protein 1ß (MIP1ß), Monocyte chemoattractant protein-3 (MCP-3), Platelet-derived growth factor bb (PDGFbb), Granulocyte-colony stimulating factor (GCSF), Fibroblast growth factor basic (bFGF), TNF-related apoptosis inducing ligand (TRAIL), and Interferon-gamma (IFN -γ) are suggested as consequences of AS in genetically prediction.No evidence of horizontal pleiotropy or heterogeneity between the genetic variants was found (P>0.05), and a leave-one-out test confirmed the stability and robustness of this association. Conclusion: These findings suggest that ßNGF, IL-1ß, and TRAIL may play a crucial role in the pathogenesis of AS. Additionally, AS may impact the expression of cytokines such as IL-12p70, IL-17, IL-6, IL-4, SDF-1α, MIP1ß, MCP-3, PDGFbb,GCSF, bFGF,TRAIL,and IFN-γ. Further investigations are warranted to determine whether these biomarkers can be utilized for the prevention or treatment of AS.

Investigation of the Mechanical Properties of Iron Tailings Concrete Subjected to Dry-Wet Cycle and Negative Temperature.

This research investigates the effects of iron tailings content on the mechanical properties and durability of concrete under dry-wet cycling and negative temperature conditions (-10 °C), where iron tailings replace river sand at rates of 0%, 10%, 20%, and 30%. A variety of tests were conducted on the iron tailings concrete, including compressive strength, flexural strength, splitting tensile strength, mass loss, and relative dynamic modulus, and its pore characteristics were analyzed using low-field nuclear magnetic resonance (NMR) experiments. The results reveal that when 20% of the river sand was replaced with iron tailings, the concrete achieved optimal splitting strength, compressive strength, and flexural strength at 28 days, improving by 0.46 MPa, 3.14 MPa, and 0.41 MPa, respectively, compared to conventional concrete. Furthermore, the concrete containing this proportion of iron tailings demonstrated superior mechanical properties and durability in both negative temperature conditions and dry-wet cycling experiments. Due to the excellent physical and chemical properties of iron tailings, they enhance the performance of concrete when incorporated in appropriate quantities. The fine granularity of iron tailings helps to compensate for the granularity defects in concrete aggregates by filling internal voids, optimizing the pore structure, and improving the concrete's density and integrity. This enhances the concrete's mechanical properties and its resistance to external solutions and harmful ion penetration. Additionally, the active substances in iron tailings promote the hydration reaction of cement, leading to the formation of an increased amount of C-S-H gel and other hydration products in the cement system.

Non-invasive manipulation scheme of spherical particle in viscous fluids in a tube based on acoustic radiation force.

A theoretical solution of the acoustic radiation force (ARF) on spherical particles by an arbitrary beam in viscous fluids in a tube is proposed. Based on the parametric design with the purpose of promoting calculi in the urinary system, theoretical solutions and finite element simulations are carried out, which mutually confirm the accuracy and feasibility of the scheme. The variation law of the ARF with adjustable parameters, such as incident angle, frequency spectrum, particle radius, tube radius, and viscosity, is studied, and the mechanism of the variation law is explained. This solution lays a foundation for the application of non-contact and non-invasive in-tube manipulation based on ARF in medicine and life sciences.

Knockdown of PVT1 Exerts Neuroprotective Effects against Ischemic Stroke Injury through Regulation of miR-214/Gpx1 Axis.

Previous studies have reported that lncRNA PVT1 was closely related to ischemic stroke. Here, the role of PVT1 in ischemic stroke and the underlying mechanism were investigated. OGDR-stimulated PC12 cells were used to construct a cell model to mimic ischemic stroke. si-PVT1, miR-214 mimic, inhibitor, or the negative controls were transfected into PC12 cells prior to OGDR treatment. PVT1, miR-214, and Gpx1 expression was measured by qRT-PCR and western blotting assays. Cell proliferation and apoptosis were tested by CCK-8 assay and western blotting. The expression levels of inflammatory factors were determined by ELISA Kit. Results showed that PVT1 was increased significantly in OGDR PC12 cells. PVT1 knockdown significantly enhanced cell viability and attenuated cell apoptosis, ROS generation, and inflammation in OGDR PC12 cells. More importantly, PVT1 or Gpx1 was a target of miR-214. Mechanistically, PVT1 acted as a competing endogenous RNA of miR-214 to regulate the downstream gene Gpx1. In conclusion, PVT1 knockdown attenuated OGDR PC12 cell injury by modulating miR-214/Gpx1 axis. These findings offer a potential novel strategy for ischemic stroke therapy.

Calycosin Alleviates Oxidative Injury in Spinal Astrocytes by Regulating the GP130/JAK/STAT Pathway.

Spinal injury is a complicated disease and is reported to be associated with damages on spinal astrocytes induced by oxidative injury. Astragali Radi, a famous traditional Chinese medicine, is reported to have promising efficacy in protecting injuries in the central nervous system. This study aims to investigate the effect of calycosin, an isoflavone phytoestrogens isolated from Astragali Radi, on oxidative injury in spinal astrocytes induced by H2O2 and the underlying mechanism. Primary rat spinal astrocytes were pretreated with 5, 10, and 20 µM calycosin and subjected to H2O2 treatment for 24 h to establish an oxidative injury model. Cell viability was detected using the CCK-8 assay to screen the optimized concentration of calycosin. Flow cytometry was used to evaluate the apoptotic rate and cell cycle. The expression level of Brdu was visualized using the immunofluorescence assay. Western blotting was used to measure the expression levels of p-JAK2, p-STAT3, p-AKT, GP130, and IL-6 in spinal astrocytes. We found that proliferation was inhibited and that apoptosis was induced by the stimulation of H2O2. The expression levels of p-JAK2, p-STAT3, p-AKT, GP130, and IL-6 were significantly elevated in H2O2-treated astrocytes. After the treatment of calycosin, proliferation was facilitated, and apoptosis was suppressed. These phenomena were accompanied by the downregulation of p-JAK2, p-STAT3, p-AKT, GP130, and IL-6, which were abolished by the co-administration of PI3K (ly294002) or STAT3 (stattic) inhibitor. Overall, calycosin alleviated oxidative injury in spinal astrocytes by mediating the GP130/JAK/STAT pathway.

Sensitive osteosarcoma diagnosis through five-base telomerase product-triggered CRISPR-Cas12a enhanced rolling circle amplification.

Osteosarcoma is the most frequent primary malignant bone tumor, composed of mesenchymal cells producing osteoid and immature bone. The sensitive detection of telomerase plays a pivotal role in the early diagnosis and therapeutic treatment of osteosarcoma. We report here an in vitro strategy for sensitive telomerase activity detection through the integration of rolling circle amplification (RCA) and a clustered regularly spaced short palindrome repeats (CRISPR)-Cas12a system. In the proposed strategy, telomerase substrate (TS) primers are easily controlled to extend five bases (GGGTT) to give short telomerase extension products (TEP) with definite lengths without adding dATP. The resulting short TEPs can then cyclize the padlock through hybridizing with its two terminals and thus initiate the following RCA. To obtain an improved sensitivity, the CRISPR-Cas12a system is attached to collaterally cut surrounding DNA reporter probes after recognizing the target single strand DNA sequence in the RCA products. The highlights of this strategy are as follows: (i) the short TEP triggered strategy is excellent at detecting low telomerase activity and thus contributes to the early diagnosis of malignant tumors; (ii) highly sensitive telomerase activity detection which is easy to operate from RCA initiated CRISPR-Cas12a; (iii) opening up of a new avenue for telomerase activity detection with a CRISPR-Cas12a system. Finally, the proposed strategy exhibited sensitive telomerase activity detection under optimized experimental parameters and has great application potential for the clinical diagnosis of malignant tumors and the development of anti-cancer drugs.

Hearing Screening Combined with Target Gene Panel Testing Increased Etiological Diagnostic Yield in Deaf Children.

Genetic testing is the gold standard for exploring the etiology of congenital hearing loss. Here, we enrolled 137 Chinese patients with congenital hearing loss to describe the molecular epidemiology by using 127 gene panel testing or 159 variant testing. Sixty-three deaf children received 127 gene panel testing, while seventy-four patients received 159 variant testing. By use of 127 gene panel testing, more mutant genes and variants were identified. The most frequent mutant genes were GJB2, SLC26A4, MYO15A, CDH23, and OTOF. By analyzing the patients who received 127 gene panel testing, we found that 51 deaf children carried variants which were not included in 159 variant testing. Therefore, a large number of patients would be misdiagnosed if only 159 variant testing is used. This study highlights the advantage of 127 gene panel testing, and it suggests that broader genetic testing should be done to identify the genetic etiology of congenital hearing loss.

Identification of Novel Compound Heterozygous MYO15A Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss.

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the MYO15A gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802_2812del/c.5681T>C and c.5681T>C/c.6340G>A in the MYO15A gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the MYO15A gene. The two novel variants, c.2802_2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the MYO15A gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness.

[Nonsyndromic deafness due to compound heterozygous mutation of the CDH23 gene].

Objective:To identify the pathogenic gene mutation of two patients with non-syndromic deafness（NSHL）. Methods:Two patient with NSHL and their parents were selected in the research object. Each participant provided 3-5 mL of peripheral venous blood, which was used to establish a DNA library. Next generation sequencing was used to detect the sequence of the patient's genome, and the sequencing results were compared with the human genome sequence （GRCh）37/hg19. Sanger sequencing was used to verify the parents' genome sequence. Finally the patient's pathogenic gene mutation was confirmed.Amino acid conservatism and single nucleotide polymorphisms of the mutant sites were analyzed using a variety of databases and software. Results:The mutation was located to CDH23 gene in the chromosomal location 10q21-q22. Complex heterozygous mutations consist of c. 1343T>C and c. 7991_7993delTCA. Parents are heterozygous carriers of a single mutation. Conclusion:The next generation sequencing technology were used to screen the pathogenic gene mutation of inherited deafness. Combined with the genetic sequencing results of parents, the specific pathogenic gene mutation of deafness patients can be identified. While the pathogenicity of complex heterozygous mutation were explained by various pathogenicity analysis methods.

F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model.

Mutations in the GJB2 gene encoding connexin26 (Cx26) protein are one of the most common causes of hereditary deafness. Previous studies have found that different Cx26-null mouse models have severe hearing loss and deformity of the organ of Corti (OC) as well as a reduction in microtubules in pillar cells (PCs). To explore the underlying mechanism of OC deformity caused by Cx26 downregulation further, we established Cx26 knockdown (KD) mouse models at postnatal days (P)0 and P8. The actin filaments contained in the pillar cells of mice in the P0 KD group were reduced by 54.85% and vinculin was increased by 22%, while the outer hair cells (OHCs) showed normal F-actin content. In the P8 KD group, PCs and OHCs of mice also showed almost normal F-actin content. The G-actin/F-actin ratio increased by 38% in the P0 KD group. No significant change was found in the mRNA or protein expression level of G-actin or the cadherin-catenin core complex in the P0 KD group at P6. Moreover, immunofluorescence showed that the intensity of LRRK2 was reduced by 97% in the P0 KD group at P6. Our results indicate that Cx26 is involved in the maturation of the cytoskeleton during the development of the OC at the early postnatal stage. The polymerization of G-actin into F-actin is prevented in Cx26 KD mice.

Clinical factors affecting prognosis of limb osteosarcoma in China: a multicenter retrospective analysis.

OBJECTIVE: This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma. METHODS: We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients' clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan-Meier analysis and Cox regression models were used to analyze the data. RESULTS: The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma. CONCLUSION: The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin-cisplatin-ifosfamide triple chemotherapy.

Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous KCNQ1 Mutation in a Chinese Family.

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

Experimental study of the difference in deformation between normal and pathological, renal and bladder, cells induced by acoustic radiation force.

Previous studies have shown that alterations in the mechanical properties of cells may be associated with the onset and progression of some forms of pathology. In this paper, an experimental study of two types of cells, renal (cancer) and bladder (cancer) cells, is described which used acoustic radiation force (ARF) generated by a high-frequency ultrasound focusing transducer and performed on the operating platform of an inverted light microscope. Comparing images of cancer cells with those of normal cells of the same kind, we find that the cancer cells are more prone to deform than normal cells of the same kind under the same ARF. In addition, cancer cells with higher malignancy are more deformable than those with lower malignancy. This means that the deformability of cells may be used to distinguish diseased cells from normal ones, and more aggressive cells from less aggressive ones, which may provide a more rapid and accurate method for clinical diagnosis of urological disease in the future.

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells.

The overall survival rate of patients with osteosarcoma has remained unchanged for the last several decades. Therefore, novel drugs for osteosarcoma treatment are required. Isoliquiritigenin (ISL), a natural compound, has been demonstrated to inhibit the growth of various tumors. However, it is unclear whether ISL is able to inhibit the growth of osteosarcoma. In the present study, it was identified that ISL was able to inhibit the growth of the osteosarcoma cell line Saos­2 cells in vitro and in xenograft tumors primarily by attenuating tumor cell proliferation and, cell migration and promoting tumor cell apoptosis. Decreased tumor cell proliferation induced by ISL was associated with downregulation of cyclin D1 and upregulation of p53, p21 and p27. Increased tumor cell apoptosis triggered by ISL was associated with downregulation of apoptosis regulator Bcl­2, upregulation of apoptosis regulator Bax and damaged mitochondrial function evidenced by a low level of ATP­synthesis. In addition, ISL was able to inhibit the migratory capacity of Saos­2 cells by modulating the expression of matrix metalloproteinase (MMP)2 and MMP9. Mechanistic analysis revealed that the tumor growth­inhibitory effect of ISL may depend on the action of ISL on the phosphorylation of PI3K and AKT. However, it remains to be investigated whether the inhibitory effect of ISL on the migration of Saos­2 cells was associated with downregulated PI3K/AKT signaling. Overall, the present study provided evidence for the potential use of ISL against osteosarcoma.

Simultaneous determination of five bioactive components of Gancao in rat plasma by UHPLC-MS/MS and its application to comparative pharmacokinetic study of incompatible herb pair Gansui-Gancao and Gansuibanxia Decoction.

Incompatible herb pair Gansui-Gancao is recorded in "eighteen incompatible" medicaments in many monographs of TCM (Traditional Chinese Medicine) which means the two herbs can not be co-used in most cases. However, Gansuibanxia decoction composed of Gansui(Kansui), Banxia(Pinellia), Shaoyao(Peony) and Gancao(Liquorice) is a traditional Chinese formula which has been clinically employed for the treatment of cancerous ascites, pleural effusion, peritoneal effusion, etc. The purpose of the study was to investigate the pharmacokinetics of main bioactive components in Gancao to explore the reasons why Gansui-Gancao can be used in Gansuibanxia decoction. A simple, rapid and sensitive UHPLC-MS/MS method for simultaneous determination of liquiritigenin, isoliquiritigenin, liquiritin, glycyrrhetinic acid and glycyrrhizic acid of liquorice in rat plasma was developed and validated. After extraction from plasma, the analytes and internal standard were separated on a C18 column with the mobile phase consisting of 0.1% acetic acid containing 0.2 mM ammonium acetate in water and acetonitrile via gradient elution. The electrospary ionization source was adopted under the multiple reaction monitoring mode. The method was succesfully applied to a comparative pharmacokinetic study of main bioactive components of Gancao in rat plasma after oral administration of the extracts of Gancao (GC), Gansui-Gancao (GS-GC), Shaoyao-Gancao (SY-GC), Gansui-Shaoyao-Gancao (GS-SY-GC) and Gansuibanxia decoction (GSBXD), respectively. The pharmacokinetic parameters had significant differences (P < 0.05) in different groups which showed that Gansui decreased the bioavailability of Gancao, while Shaoyao increased the bioavailability of Gancao. Hence, these may be the pharmacokinetic mechanism of incompatible herb pair Gansui-Gancao and the reasons why the herb pair can be used in Gansuibanxia decoction.

SLC34A2 Regulates the Proliferation, Migration, and Invasion of Human Osteosarcoma Cells Through PTEN/PI3K/AKT Signaling.

Osteosarcoma (OS) is a bone malignancy with high incidence. The underlying molecular mechanisms that are associated with the development of OS need further investigation. In this study, we showed that SLC34A2, a member of the solute carrier gene family, was significantly downregulated in OS patients and cell lines. Overexpression of SLC34A2 inhibited the proliferation, migration, and invasion of OS cells. Mechanistically, we found that SLC34A2 interacted with PTEN, and inactivated the PI3K/AKT signaling pathway. Collectively, our results demonstrated that SLC34A2 plays important roles in regulating the cancer cell growth of OS. The downregulation of SLC34A2 in OS patients suggested that it might be a promising target in the diagnosis and therapy of OS.

Fat-Soluble Vitamin Deficiency in Pediatric Patients with Biliary Atresia.

OBJECTIVE: To analyze the levels of fat-soluble vitamins (FSVs) in pediatric patients with biliary atresia (BA) before and after the Kasai procedure. METHODS: Pediatric patients with obstructive jaundice were enrolled in this study. The FSV levels and liver function before, 2 weeks after, and 1, 3, and 6 months after the Kasai procedure were measured. RESULTS: FSV deficiency was more obvious in patients with BA than in patients with other cholestatic liver diseases, especially vitamin D deficiency. 25-Hydroxy vitamin D (25-(OH)D) deficiency was more pronounced in younger patients before surgery. The 25-(OH)D level was significantly higher in patients with than without resolution of jaundice 3 months after surgery. At 6 months after surgery, the 25-(OH)D level was abnormally high at 8.76 ng/ml in patients with unresolved jaundice. CONCLUSIONS: Preoperative FSV deficiency, particularly vitamin D deficiency, is common in patients with BA. 25-(OH)D deficiency is more pronounced in younger children before surgery. Postoperative FSV deficiency was still prevalent as shown by the lower 25-(OH)D levels in patients with BA and unresolved jaundice. This required long-term vitamin AD supplementation for pediatric patients with BA and unresolved jaundice after surgery.

Knockdown of E2F3 Inhibits Proliferation, Migration, and Invasion and Increases Apoptosis in Glioma Cells.

E2F3a, as a member of the E2F family, is essential for cell division associated with the progression of many cancers. However, the biological effect of E2F3a on glioma is not understood as well. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissue and cell lines. We found that E2F3a was upregulated in glioma tissue compared with adjacent tissue, and this was associated with a poor survival rate. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines. Knockdown of E2F3a significantly inhibited cell proliferation, promoted G0/G1 phase arrest, elevated apoptosis rates, and suppressed cell migration and invasion. However, overexpression of E2F3a markedly promoted cell proliferation, migration, and invasion and inhibited apoptosis. Moreover, in vivo studies showed that knockdown of E2F3a expression dramatically inhibited U373 tumor growth in a nude mouse model. Results of real-time PCR and Western blot showed that the depletion of E2F3a upregulated the expression levels of cell apoptosis-related proteins and downregulated migration-related proteins. Conversely, E2F3a overexpression downregulated the expression levels of cell apoptosis-related proteins and upregulated migration-related proteins. In conclusion, our results highlight the importance of E2F3a in glioma and provide new insights into the diagnostics and therapeutics of gliomas.

Personalized Identification of Differentially Expressed Modules in Osteosarcoma.

BACKGROUND Osteosarcoma (OS), an aggressive malignant neoplasm, is the most common primary bone cancer mainly in adolescents and young adults. Differentially expressed modules tend to distinguish differences integrally. Identifying modules individually has been crucial for understanding OS mechanisms and applications of custom therapeutic decisions in the future. MATERIAL AND METHODS Samples came from individuals were used from control group (n=15) and OS group (n=84). Based on clique-merging, module-identification algorithm was used to identify modules from OS PPI networks. A novel approach - the individualized module aberrance score (iMAS) was performed to distinguish differences, making special use of accumulated normal samples (ANS). We performed biological process ontology to classify functionally modules. Then Support Vector Machine (SVM) was used to test distribution results of normal and OS group with screened modules. RESULTS We identified 83 modules containing 2084 genes from PPI network in which 61 modules were significantly different. Cluster analysis of OS using the iMAS method identified 5 modules clusters. Specificity=1.00 and Sensitivity=1.00 proved the distribution outcomes of screened modules were mainly consistent with that of total data, which suggested the efficiency of 61 modules. CONCLUSIONS We conclude that a novel pipeline that identified the dysregulated modules in individuals of OS. The constructed process is expected to aid in personalized health care, which may present fruitful strategies for medical therapy.