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OBJECTIVE@#To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism.@*METHODS@#Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene.@*RESULTS@#The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain.@*CONCLUSION@#The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.
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Animals , Male , Mice , Autism Spectrum Disorder/genetics , Epilepsy/genetics , Mutation , Mutation, Missense , Protein Kinases , Protein Serine-Threonine Kinases/genetics , Exome SequencingABSTRACT
Objective:To study whether aspirin has inhibitory effect on microglia activation induced by Poly-IC and its mechanism.Methods:Microglia cell line BV2 were cultured in vitro to establish a Poly-IC stimulation-induced microglia cell immune activation model. The experiment groups were divided into control group (no treatment), model group (Poly-IC 10 μg/ml), high dose aspirin group (1 mmol/L aspirin), low dose aspirin group (0.1 mmol/L aspirin), high dose aspirin pretreatment group (Poly-IC 10 μg/ml + 1 mmol/L aspirin) and low dose aspirin pretreatment group (Poly-IC 10 μg/ml + 0.1 mmol/L aspirin). The phagocytosis ability of microglia cells, reactive oxygen species (ROS) and Iba1 protein expression were detected by using immunofluorescence method. The expression of the inflammatory cytokines Il-1β, Il-6, Il-10, TNF-α and cox-2 mRNA in microglia cells were detected by real-time quantitative PCR (RT-qPCR).Results:Compared with the control group, the morphology of microglia cells in model group changed significantly, and the phagocytosis ability and production of reactive oxygen species (ROS) increased. At the meantime, the expression of Iba1 protein was strongly decreased. In the model group, The mRNA expressions of IL-1β(20.55±1.92), IL-6 (63.98±7.83), TNF-α (16.84±3.19), COX-2 (6.78±0.42) were higher than IL-1β(1.01±0.14), IL-6 (0.95±0.17), TNF-α (1.22±0.38), COX-2 (0.87±0.11) in the control group. (Il-1β ( t=26.14), Il-6 ( t=10.22), TNF-α ( t=17.06) and COX-2 ( t=37.07), all P<0.01). In the aspirin pretreatment group, the phagocytic ability of microglia cells was inhibited compared with the model group, and the production of reactive oxygen species (ROS) reduced. The expression of Iba1 protein was also partly recovered. Meanwhile, the effect of the high aspirin dose pretreatment group on pro-inflammatory factors IL-1β(9.95±0.52), IL-6 (39.64±6.89), TNF-α(1.57±0.42), COX-2 (2.47±0.14)were lower than those in the model group significantly.(IL-1β: t=14.18, IL-6: t=3.69, TNF-α: t=16.68, COX-2: t=27.03, all P<0.01). Conclusion:Aspirin has an inhibitory effect on microglial activation induced by Poly-IC, which may be related with inhibiting the expression of inflammatory factors.
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BACKGROUND: Studies have shown that osteoporosis often leads to a failure in pedicle screw fixation. Considering that the use of ordinary pedicle screw fixation cannot achieve a strong and stable fixation of the osteoporotic vertebra,special measures to strengthen the internal fixation is indispensable.OBJECTIVE: To evaluate the effect of bone cement augmentation combined with expandable pedicle screw fixation on the fixation strength of osteoporotic thoracolumbar vertebrae.METHODS: Twenty osteoporotic thoracolumbar vertebral specimens were randomly divided into four groups: conventional pedicle screw group implanted with normal pedicle screw, and the other three groups implanted with expandable pedicle screw. Bone cement augmentation with polymethylmethacrylate (PMMA) and calcium sulfate was done in the PMMA group and calcium sulfate group, respectively, followed by expandable pedicle screw implantation. No bone cement was used in the expandable pedicle screw group. The maximum axial pull-out strength and yield energy absorption value of the unilateral pedicle were detected, and the maximum removal torque of the contralateral pedicle was determined. Bone cement leakage after augmentation was observed.RESULTS AND CONCLUSION: Compared with the conventional pedicle screw group, the other three groups showed a significant increase in the maximum pull-out strength, maximum removal torque and yield energy absorption values (P 0.05). No leakage of bone cement was found in all the groups. To conclude, the combined use of expandable pedicle screw and can significantly enhance the stability of the osteoporotic thoracolumbar vertebrae, and the PMMA and calcium sulfate cements have similar effects.
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BACKGROUND:We built Sprague-Dawley rat models with mild, moderate, and severe spinal cord injuries to accord with the spinal cord injury types for basic empirical study, and consequently to further understand the microenvironmental change in Sprague-Dawley rats with spinal cord injury, and to provide help for clinical treatment. OBJECTIVE:To observe the changes in nerve function, pathological manifestation and motor sensory evoked potential in Alen’s models and Sprague-Dawley rats with complete spinal cord transection at different time points after spinal cord injury by simulating the microenviroment in Sprague-Dawley rats. METHODS: A total of 125 healthy adult female Sprague-Dawley rats were selected and randomly divided into group sham operation group, 100 gcf hit potential group (20 g×5 cm), 200 gcf hit potential (20 g×10 cm), 300 gcf hit potential group (20 g×15 cm), and spinal cord complete transection group with 25 rats in each group. At 1, 5, 7, 14 and 28 days after model establishment, the degree of spinal cord injury was identified by the BBB scores of motion function, motor evoked potential, and pathological section. RESULTS AND CONCLUSION:(1) Totaly 24 Sprague-Dawley rats died in the experiment. The death rate and the rate of complications were highest in the spinal cord complete transection group. The BBB score of each group was decreased. The BBB scores in every group increased as time went on. There were significant differences between each surgery group and the sham operation group at corresponding time points (P 0.05). (2) In each surgery group, the infiltration of inflammatory cels and obvious sweling of neurons were visible at 1 day after injury. Neural cels reduced with time prolonged. At 28 days after injury, a large number of astrocytes proliferated, scar and spinal cord cavity formed. Above symptoms were worse in the 300 gcf hit potential group and spinal cord complete transection group than in the 100 gcf and 200 gcf hit potential groups. (3) Significant differences in amplitude and latency were detectable between each surgery group and the sham operation group (P 0.05). Results confirmed that hit potential of 20 g×5 cm, 20 g×10 cm and 20 g×15 cm can simulate the microenvironment of Sprague-Dawley rats with mild, moderate and severe spinal cord injury. The rate of complication was lower in modified Alen’s model of different hit potentials than in models of spinal cord complete transection, and was more accorded with basic research.
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BACKGROUND:Transformation growth factor beta 1 is mostly used to induce the chondrogenic differentiation of bone marrow mesenchymal stem cel s, but there is a poor induction efficacy. OBJECTIVE:To explore the chondrogenic differentiation of bone marrow mesenchymal stem cel s co-cultured with articular chondrocytes or induced by transforming growth factor beta 1. METHODS:Articular chondrocytes and bone marrow mesenchymal stem cel s from SD rats were harvested and divided into 1:2, 2:1, 1:1 concentration groups. Cel s induced by transforming growth factor beta 1 acted as control group. After 20 days of induced culture, MTT was used to detect cel viability, alcian blue colorimetric assay was applied to measure glycosaminoglycan content, and western blot assay was employed to determine the expression of col agen type II. RESULTS AND CONCLUSION:The absorbance value in the control group was significantly lower than that in the 1:1 and 2:1 groups (P0.05). The results show that bone marrow mesenchymal stem cel s co-cultured with articular chondrocytes can be induced to differentiate into chondrocytes, and meanwhile, there is a saturation phenomenon during the chondrogenic differentiation of bone marrow mesenchymal stem cel s.
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Objective To investigate the clinical therapeutic effects of different surgical treatments on cervical spondylotic my-elopathy and the occurrence of postoperative complications .Methods 65 patients with cervical spondylotic myelopathy admitted in our department between January 2010 and January 2013 were retrospectively analyzed ;and among them ,31 underwent anterior cer-vical discectomy and fusion(ACDF) and 34 underwent anterior cervical corpectomy and fusion (ACCF);the general surgical condi-tions ,JOA scores and functional grades of Nurick ,incidences of dysphagia and so on in the patients of the two groups were investi-gated .Results The operative time and intra-operative blood loss of the patients of the ACDF group were better than those of the ACCF group[(88 .70 ± 9 .03)min ,(125 .46 ± 12 .62)min ,(94 .26 ± 10 .34)mL ,(133 .98 ± 12 .09)mL] ,and the differences were sta-tistically significant(P0 .05);but the differences between the preoperative and postoperative JOA scores and functional grade of Nurick in 6 months after the surgeries and those before the surgeries of the same groups were statistically significant (P<0 .05) .At the same observation time points ,the incidences of dysphagia and the thicknesses of soft tissue before the cervical vertebra in the operated segment of the observation group were all lower than those of the control group ,and the differences were statistically significant (P<0 .05);in the patients of either group ,no loosening ,translocation or non-fusion of the bone graft was observed .Conclusion The two surgeries in treatment of cervical spondylotic myelopathy van both obtain satisfying clinical therapeutic effects ,but ACDF has a lower incidence of postop-erative complications ,and doctors should choose a suitable surgery based on the actual conditions .
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Objective To investigate the effects of preemptive analgesia with parecoxib sodium on postoperative analgesia and delirium after nerve injury-free surgery for fracture of thoracic and lumbar vertebrae and to promote the postoperative rehabilitation of the patients. Method 80 patients meeting the criteria were selected. and randomly divided into observation group and control group.40 patients each group. The observation group used parecoxib sodium for preemptive analgesia. while the control group used sufentanil. and the analgesia effects and the incidences of delirium were observed. Results The differences in operative time and intra-operative blood loss between the patients of the two groups were statistically insignificant. In 2 h. 6 h. 12 h.24 h and 48 h after the surgery.the VAS score and the accumulative time of intravenous self-controlled analgesia pump being pressed of the observation group were significantly lower than those of the control group. and the differences were statistically significant (P<0.05). The first time for the patients of the observation group to press the intravenous self-controlled analgesia pump is (3.84±0.62) h after the surgery, is significantly later than that of the control group (1.05±0.47)h.and the difference is statistically significant (P<0.05). The incidence of delirium in 7 days after the surgery in the patients of the observation group was 10.00%. and is significantly lower than that of the control group (25.00%) (P<0.05). Conclusion Using parecoxib sodium for preemptive analgesia before nerve injury-free surgery for fracture of thoracic and lumbar vertebrae can elevate the postoperative analgesia effects of the patients.decrease the incidence of postoperative delirium, and is highly safe and consequently worthy of clinical application.