Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.

Combined computational analysis and cytology show limited depth osteogenic effect on bone defects in negative pressure wound therapy.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.

[Finite element analysis of different intramedullary fixation methods for the treatment of senile pubic ramus fractures].

OBJECTIVE: To evaluate the biomechanical stability of elastic intramedullary nail in the treatment of pubic ramus fractures by finite element analysis, and to compare the stability of elastic intramedullary nail with cannulated screw intramedullary fixation. METHODS: The CT data of the pelvis of a volunteer were selected, and the three-dimensional model of the pelvis was reconstructed by reverse engineering software and the fracture of the pubic ramus fractures was simulated by osteotomy. The hollow nail model, single elastic nail model and double elastic nailmodel were assembled with different implants respectively. The mesh division, material assignment loading and other steps were carried out in the ANSYS software, and then the calculation was submitted. RESULTS: The overall displacement of the pelvis of the elastic nail model was smaller than that of the cannulated screw model, in which the double elastic nail model had the smallest overall displacement, but the cannulated screw model had the smallest plant displacement and the single elastic nail model had the largest plant displacement. Although the stress of cannulated screw was small, there was obvious stress concentration, the stress of elastic nail was large, but there was no obvious stress concentration, especially the stress distribution of double elastic nail was more uniform and the overall stress of pelvis was the smallest. CONCLUSION: All the three fixation methods can effectively improve the stability of the anterior ring of the pelvis. Among them, there is no significant difference in the overall biomechanical propertiesof hollow nail fixation and double elastic nail fixation, which is better than that of single elastic nail fixation. Elastic nail fixation has the advantages of minimally invasive surgery and good biomechanical stability, so it can be used as a better surgical method for the treatment of pubic ramus fractures.

[Low level laser irradiation in the visible spectra induces HeLa cells proliferation].

The aim of this in vitro study was to evaluate the effects of low level laser irradiation on the proliferation of HeLa cells using 405 nm diode laser, 514 nm argon laser, 633 nm He-Ne laser, or 785 nm diode laser, The cells were seeded on 96-well microplates for 24 h in 5% fetal bovine serum containing medium, then irradiated with the laser at dose of 100 and 1 000 J x m(-2), respectively. At the time point of 24, 48, 72 h after irradiation, cell viability was assessed by MTT assay. The results show that 405, 633 and 785 nm laser irradiation induces wavelength-dependent and time-dependent proliferation. 633 nm laser irradiation results in a stimulatory proliferation effect that is most significant, whereas 514 nm laser irradiation produces little increase in cell proliferation. Low level laser irradiation increases cell proliferation in a dose-dependent manner. 1 000 J x m(-2) laser irradiation is more effective in increasing cell proliferation than 100 J x m(-2) laser irradiation using 405 nm diode laser, 633 nm He-Ne laser, or 785 nm diode laser, but not as effective as using 514 nm argon laser.