Objective:To evaluate the effect of dexmedetomidine on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in the hippocampus of mice with cognitive impairment after traumatic brain injury (TBI).Methods:Sixty specific pathogen-free healthy adult wild-type C57BL/6 mice, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=12 each) by a random number table method: sham operation + vehicle group (SV group), sham operation + dexmedetomidine group (SD group), TBI + vehicle group (TV group), TBI + dexmedetomidine group (TD group) and TBI + TLR4 inhibitor TAK-242 group (TT group). The modified Feeney free fall epidural impact method was used to establish a mild TBI model. At 30 min before model preparation, dexmedetomidine 25 μg/kg was intraperitoneally injected in SD group and TD group, TAK-242 10 mg/kg was intraperitoneally injected in TT group, and the equal volume of normal saline was intraperitoneally injected in SV group and TV group. Neurological severity scores (NSSs) were used to evaluate the neurological function at 1, 7 and 14 days after developing the model. The novel object recognition test (recognition index) and fear conditioning test (the percentage of freezing time related to context and sound) were used to evaluate the cognitive function of mice at 16 days after developing the model. The number and morphology of hippocampal neurons (NeuN-positive cells) and activated microglia (ionized calcium-binding adaptor molecule 1[IBA1]-positive cells) were measured by immunofluorescent staining. The expression of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), TLR4, MyD88 and nuclear factor kappa B (NF-κB) was detected by Western blot. Results:Compared with SV group, the NSS was significantly increased, the recognition index was decreased, the percentage of freezing time related to context and sound was decreased, the number of NeuN-positive cells was decreased, the number of IBA1-positive cells was increased and the cell body area was enlarged, the total branch length and intersection points were decreased, and the expression of TLR4, MyD88, NF-κB, IL-1β, IL-6 and TNF-α was up-regulated in TV group ( P<0.05). Compared with TV group, the NSS was significantly decreased, the recognition index was increased, the percentage of freezing time related to context and sound was increased, the number of NeuN-positive cells was increased, the number of IBA1-positive cells was decreased and the cell body area was reduced, the total branch length and intersection points were increased, and the expression of TLR4, MyD88, NF-κB, IL-1β, IL-6 and TNF-α was down-regulated in TD group and TT group ( P<0.05). There was no statistically significant difference in the aforementioned parameters between TD group and TT group ( P>0.05). Conclusions:The mechanism by which dexmedetomidine mitigates TBI-induced cognitive impairment may be related to inhibition of the hippocampal TLR4/MyD88/NF-κB signaling pathway and reduction of neuroinflammatory responses in mice.

Objective:To explore the effects of astragaloside (Ast) on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and excitation-inhibition balance in amygdala of mice with autism spectrum disorder(ASD).Methods:The C57BL/6 pregnant mice in model group were intraperitoneally injected with sodium valproate(500 mg/kg) on days 12-13 of pregnancy, while the C57BL/6 pregnant mice in control group were given an equal volume of 0.9% NaCl solution.The offspring mice were then divided into 5 groups according to the nest matching principle: the control+ normal saline group(Con+ NS group), the control+ Ast group (Con+ Ast group), the model+ normal saline group(Mod+ NS group), the model+ Ast group (Mod+ Ast group) and the Model+ Ast+ PI3K inhibitor LY294002 group (Mod+ Ast+ LY group), with 12 mice in each group. At the age of 14 days, the mice in the Con+ Ast group and the Mod+ Ast group were intraperitoneally injected with Ast (20 mg/kg, once a day for 7 consecutive days), the mice in the Mod+ Ast+ LY group were intraperitoneally injected with Ast (20 mg/kg) and LY294002(30 mg/kg), the mice in Con+ NS group and Mod+ NS group were intraperitoneally injected with the same volume of 0.9% NaCl solution.The depressive-like behavior and social function were evaluated by the marble-burying test (MBT), the three-chamber social interaction test(SIT), and the forced swimming test(FST). The expression levels of proteins related to the PI3K/AKT signaling pathway in the amygdala were detected by Western blot. The immunofluorescence method was employed to determine the levels of the neurotransmitters glutamate (Glu) and γ-aminobutyric acid(GABA)in the amygdala region.Statistical analysis was carried out using GraphPad Prism 9.5.0 software, and one-way ANOVA test was utilized for comparisons among multiple groups.Results:(1)Behavioral results showed that there were statistically significant differences in the number of buried beads of the MBT, the social interaction index and social novelty preference index of the SIT, and the immobility time and first immobile state incubation period of the FST among the five groups( F=28.85, 89.23, 77.62, 91.70, 125.40, all P<0.05). The number of buried beads and immobility time in Mod+ NS group were higher than those in Con+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Con+ NS group (all P<0.05). The number of buried beads and immobility time in Mod+ Ast group were lower than those in Mod+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were higher than those in Mod+ NS group(all P<0.05). The number of buried beads and immobility time in Mod+ Ast+ LY group were higher than those in Mod+ Ast group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Mod+ Ast group (all P<0.05).(2) Western blot results showed that there were statistically significant differences in p-PI3K/PI3K, p-AKT/AKT in amygdala among the five groups ( F=27.14, 25.50, both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ NS group were lower than those of Con+ NS group(both P<0.05).The expressions of p-PI3K/PI3K and p-AKT/AKT in amygdala of Mod+ Ast group((0.67±0.04), (0.52±0.09))were higher than those of Mod+ NS group((0.48±0.06), (0.34±0.06))(both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ Ast+ LY group ((0.52±0.04), (0.36±0.10))were lower than those of Mod+ Ast group(both P<0.05). (3)Immunofluorescence results showed that the number of Glu- and GABA- positive cells in the amygdala region of the five groups were significantly different( F=41.84, 37.70, both P<0.05). The number of Glu-positive cells in the amygdala of Mod+ NS group was higher than that of Con+ NS group, and the number of GABA-positive cells in Mod+ NS group was lower than that of Con+ NS group( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast group((54.00±8.48)cells/mm 2)was lower than that of Mod+ NS group((82.17±7.36)cells/mm 2), and the number of GABA-positive cells in Mod+ Ast group((59.20±11.22)cells/mm 2)was higher than that of Mod+ NS group((41.33±7.11)cells/mm 2) ( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast+ LY group((75.67±9.15)cells/mm 2) was higher than that of Mod+ Ast group, and the number of GABA-positive cells in Mod+ Ast+ LY group((43.33±4.27)cells/mm 2)was lower than that of Mod+ Ast group ( P<0.05). Conclusion:Astragaloside can ameliorate social deficits in ASD mice via modulating the PI3K/AKT signaling pathway and excitation-inhibition balance in the amygdala.

Objective:To explore the effects of astragaloside (Ast) on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and excitation-inhibition balance in amygdala of mice with autism spectrum disorder(ASD).Methods:The C57BL/6 pregnant mice in model group were intraperitoneally injected with sodium valproate(500 mg/kg) on days 12-13 of pregnancy, while the C57BL/6 pregnant mice in control group were given an equal volume of 0.9% NaCl solution.The offspring mice were then divided into 5 groups according to the nest matching principle: the control+ normal saline group(Con+ NS group), the control+ Ast group (Con+ Ast group), the model+ normal saline group(Mod+ NS group), the model+ Ast group (Mod+ Ast group) and the Model+ Ast+ PI3K inhibitor LY294002 group (Mod+ Ast+ LY group), with 12 mice in each group. At the age of 14 days, the mice in the Con+ Ast group and the Mod+ Ast group were intraperitoneally injected with Ast (20 mg/kg, once a day for 7 consecutive days), the mice in the Mod+ Ast+ LY group were intraperitoneally injected with Ast (20 mg/kg) and LY294002(30 mg/kg), the mice in Con+ NS group and Mod+ NS group were intraperitoneally injected with the same volume of 0.9% NaCl solution.The depressive-like behavior and social function were evaluated by the marble-burying test (MBT), the three-chamber social interaction test(SIT), and the forced swimming test(FST). The expression levels of proteins related to the PI3K/AKT signaling pathway in the amygdala were detected by Western blot. The immunofluorescence method was employed to determine the levels of the neurotransmitters glutamate (Glu) and γ-aminobutyric acid(GABA)in the amygdala region.Statistical analysis was carried out using GraphPad Prism 9.5.0 software, and one-way ANOVA test was utilized for comparisons among multiple groups.Results:(1)Behavioral results showed that there were statistically significant differences in the number of buried beads of the MBT, the social interaction index and social novelty preference index of the SIT, and the immobility time and first immobile state incubation period of the FST among the five groups( F=28.85, 89.23, 77.62, 91.70, 125.40, all P<0.05). The number of buried beads and immobility time in Mod+ NS group were higher than those in Con+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Con+ NS group (all P<0.05). The number of buried beads and immobility time in Mod+ Ast group were lower than those in Mod+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were higher than those in Mod+ NS group(all P<0.05). The number of buried beads and immobility time in Mod+ Ast+ LY group were higher than those in Mod+ Ast group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Mod+ Ast group (all P<0.05).(2) Western blot results showed that there were statistically significant differences in p-PI3K/PI3K, p-AKT/AKT in amygdala among the five groups ( F=27.14, 25.50, both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ NS group were lower than those of Con+ NS group(both P<0.05).The expressions of p-PI3K/PI3K and p-AKT/AKT in amygdala of Mod+ Ast group((0.67±0.04), (0.52±0.09))were higher than those of Mod+ NS group((0.48±0.06), (0.34±0.06))(both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ Ast+ LY group ((0.52±0.04), (0.36±0.10))were lower than those of Mod+ Ast group(both P<0.05). (3)Immunofluorescence results showed that the number of Glu- and GABA- positive cells in the amygdala region of the five groups were significantly different( F=41.84, 37.70, both P<0.05). The number of Glu-positive cells in the amygdala of Mod+ NS group was higher than that of Con+ NS group, and the number of GABA-positive cells in Mod+ NS group was lower than that of Con+ NS group( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast group((54.00±8.48)cells/mm 2)was lower than that of Mod+ NS group((82.17±7.36)cells/mm 2), and the number of GABA-positive cells in Mod+ Ast group((59.20±11.22)cells/mm 2)was higher than that of Mod+ NS group((41.33±7.11)cells/mm 2) ( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast+ LY group((75.67±9.15)cells/mm 2) was higher than that of Mod+ Ast group, and the number of GABA-positive cells in Mod+ Ast+ LY group((43.33±4.27)cells/mm 2)was lower than that of Mod+ Ast group ( P<0.05). Conclusion:Astragaloside can ameliorate social deficits in ASD mice via modulating the PI3K/AKT signaling pathway and excitation-inhibition balance in the amygdala.

Objective:To evaluate the effect of dexmedetomidine on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in the hippocampus of mice with cognitive impairment after traumatic brain injury (TBI).Methods:Sixty specific pathogen-free healthy adult wild-type C57BL/6 mice, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=12 each) by a random number table method: sham operation + vehicle group (SV group), sham operation + dexmedetomidine group (SD group), TBI + vehicle group (TV group), TBI + dexmedetomidine group (TD group) and TBI + TLR4 inhibitor TAK-242 group (TT group). The modified Feeney free fall epidural impact method was used to establish a mild TBI model. At 30 min before model preparation, dexmedetomidine 25 μg/kg was intraperitoneally injected in SD group and TD group, TAK-242 10 mg/kg was intraperitoneally injected in TT group, and the equal volume of normal saline was intraperitoneally injected in SV group and TV group. Neurological severity scores (NSSs) were used to evaluate the neurological function at 1, 7 and 14 days after developing the model. The novel object recognition test (recognition index) and fear conditioning test (the percentage of freezing time related to context and sound) were used to evaluate the cognitive function of mice at 16 days after developing the model. The number and morphology of hippocampal neurons (NeuN-positive cells) and activated microglia (ionized calcium-binding adaptor molecule 1[IBA1]-positive cells) were measured by immunofluorescent staining. The expression of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), TLR4, MyD88 and nuclear factor kappa B (NF-κB) was detected by Western blot. Results:Compared with SV group, the NSS was significantly increased, the recognition index was decreased, the percentage of freezing time related to context and sound was decreased, the number of NeuN-positive cells was decreased, the number of IBA1-positive cells was increased and the cell body area was enlarged, the total branch length and intersection points were decreased, and the expression of TLR4, MyD88, NF-κB, IL-1β, IL-6 and TNF-α was up-regulated in TV group ( P<0.05). Compared with TV group, the NSS was significantly decreased, the recognition index was increased, the percentage of freezing time related to context and sound was increased, the number of NeuN-positive cells was increased, the number of IBA1-positive cells was decreased and the cell body area was reduced, the total branch length and intersection points were increased, and the expression of TLR4, MyD88, NF-κB, IL-1β, IL-6 and TNF-α was down-regulated in TD group and TT group ( P<0.05). There was no statistically significant difference in the aforementioned parameters between TD group and TT group ( P>0.05). Conclusions:The mechanism by which dexmedetomidine mitigates TBI-induced cognitive impairment may be related to inhibition of the hippocampal TLR4/MyD88/NF-κB signaling pathway and reduction of neuroinflammatory responses in mice.

Objective:To evaluate the relationship between the mechanism by which aucubin improved attention deficit hyperactivity disorder (ADHD) induced by maternal exposure to S-ketamine and GABAergic neurons in the habenular nucleus of offspring mice.Methods:SPF healthy C57BL/6 wild-type pregnant mice were used in this study, and an ADHD model in offspring mice was established by intraperitoneally injecting S-ketamine in the middle and late pregnancy. Twenty-four offspring of pregnant mice exposed to S-ketamine were divided into 2 groups ( n=12 each) at 14 days after birth using a random number table method: ADHD + normal saline group (AN group) and ADHD + aucubin group (AA group). Twenty-four offspring of pregnant mice exposed to normal saline were divided into 2 groups ( n=12 each) at 14 days after birth by a random number table method: control + normal saline group (CN group) and control + aucubin group (CA group). Aucubin 40 mg/kg was intraperitoneally injected once a day for 7 consecutive days in CA group and AA group, and the equal volume of normal saline was given instead in CN group and AN group. At 14 days after birth, the 16-channel microfilament array electrode was placed in the habenular nucleus, and the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was recorded when the mice buried beads in the marble burying test. At 21 days after birth (after the end of peritoneal administration), the impulsive and stereotypical behaviors of offspring mice were evaluated by elevated zero maze and marble burying test, respectively, and then the expression of glutamate decarboxylase 2 (GAD2) in habenular nucleus was detected by the immunofluorescence method. Results:Compared with CN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly increased, the expression of GAD2 was down-regulated, the time spent in the open arm was prolonged, the number of entries into the open arm and the number of buried beads were increased in AN group ( P<0.05), and no statistically significant differences were found in the above indexes in CA group ( P>0.05). Compared with AN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly decreased, the expression of GAD2 was up-regulated, the time spent in the open arm was shortened, and the number of entries into the open arm and the number of buried beads were decreased in AA group ( P<0.05). Conclusions:The mechanism by which aucubin alleviates prenatal S-ketamine exposure-induced ADHD may be related to increasing the number of GABAergic neurons in the habenular nucleus of offspring mice.

Objective To investigate the clinical efficacy of our self-designed sight used to guide thoracic vertebroplasty.Methods A retrospective analysis was conducted of the 52 patients (70 thoracic vertebrae) who had undergone percutaneous vertebroplasty (PVP) (n =36)or percataneous kyphoplasty (PKP) (n =34) of T1-T4 vertebral bodies at Department of Orthopaedics,The First Affiliated Hospital to Zhengzhou University form August 2012 to October 2013.The operation time,intraoperative bleeding,intraoperative radiation by C-arm roentgenography,and visual analogue scale (VAS) were compared between the patients whose surgery had been guided by our self-designed sight and those whose surgery had been not.Results All the patients were followed up for 18 to 36 months (average,22.3 months).Compared with those who had not used the sight,the patients who had used the sight incurred significantly shorter operation time (16.5 ± 3.2 min versus 26.5 ± 3.7 min),significantly less intraoperative bleeding (2.8 ± 1.3 mL versus 6.3 ± 1.7 mL) and significantly less radiation by C-arm roentgenography (5.6 ± 3.3 times versus 9.4 ± 3.1 times) (P ＜0.05).The VAS scores at postoperative 3 days and final follow-up were significantly decreased than the preoperative values in all the patients (P ＜ 0.05).There were no significant differences between the patients who had used the sight and those who had not in the the VAS scores at postoperative 3 days or final follow-up (P ＞ 0.05).Conclusions The upper thoracic PVP or PKP guided by our self-designed sight has theadvantages of short operation time,less intraoperative bleeding and less frequency of C-arm radiation.The sight is suitable for various vertebroplasties.

Objective To compare lateral orbital keyhole approach(LOK) with conventional keyhole approach including supraorbital keyhole approach (SOK) and pterional approach(PTK) for exposuring the sellar region and oper-ation ability, to provide theoretical and practical basis for the clinic. Methods From January, 2017 to Feburary, 2018, 15 cadaver head specimens of Chinese (30 sides) fixed by formalin were randomly divided into 3 groups, simu-lating SOK, LOK and PTK, application of frameless neuronavigation system, intersection of the posterior margin of the optic chiasma and the lamina terminalis served as the base point. Six different reference points were selected to radi-ate into the parasellar region of the skull base. The direction of the 2 adjacent reference points were connected to the base point to form a triangle. Six triangles constituted the sellar region to represent the total area. The supratentorial area, ipsilateral area, inferior area and contralateral area were calculated by stacking triangle. The comparison was made between groups. The Salma operation exposure scale was used to simulate the aneurysms of the common parts in the brain and the quantitative scores were performed. Results The total parasellar regions by SOK, LOK and PTK respectively were:(1641.6±295.6)mm2, (1782.3±294.6)mm2 and (1552.5±307.4)mm2. There was no statistical differ-ence(P>0.05); To compare the supratentorial region, SOK and LOK were both bigger than PTK ( P<0.05); To compare the ipsilateral and infratentorial area, LOK and PTK were both bigger than SOK respectively ( P<0.05);To compare the contralateral area, SOK, LOK and PTK were increased in turn (P<0.05). Salma operation exposure scale was used to get the scores:the score of SOK was 29.7 (39.08％), LOK was 37.0 (48.68％), and PTK was 36.1 (47.50％). Conclusion Anatomical analysis displayed that the 3 keyhole approaches showed different exposure of each part the parasellar re-gions, the LOK had a good exposure to the parasellar region and so as the higher maneuverability. But the clinical appli-cation should be comprehensive analysis, pay attention to specific lesions and make an appropriate choice. It has impor-tant clinical significance to improve the prognosis of patients.

Objective To analyse the CT,MRI features of pleomorphic xanthoastrocytoma and improve the diagnosis.Methods Imaging feature of pleomorphic xanthoastrocytoma of 26 cases confirmed by surgery and pathology were analyzed retrospectively.Distribution,size,shape,signal,dense,peritumor edema and invasion of adjacent structures of lesion were summarized.Results The locations of lesions included:temporosphenoid lobe (19 cases),frontal lobe (2 cases),the lateral and three ventricles in 1 case,occipital lobe (1 case),medulla oblongata (1 case),and cervical cord (1 case).The tumor size:maximum:82 mm × 40 mm × 70 mm,minimum:16 mm × 13 mm × 14 mm.Solid lesions (3 cases),solid lesions with necrosis (7 cases),solid and cystic lesions (16 cases),lesion with calcification (4 cases).The solid lesions of the tumors showed equal signal intensity or slightly low signal intensity on T1WI,and equal signal intensity or slightly high signal intensity on T2WI.The equidensite and high density on CT,peritumor edema degree:mild (2 cases),moderate (5 cases),severe (1 case).Conclusion The characteristic imaging features can help in the understanding and diagnosis of pleomorphic xanthoastrocytoma.