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 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 investigate the clinical value of 18F-FDG PET/CT image in assisting CT-guided puncture of pancreatic tumor.Methods One hundred and thirteen patients with pancreatic tumors were selected and then divided into 18 F-FDG PET/CT image-assisted CT-guided group(abbreviation 18F-FDG PET/CT-assisted group)(n=54)and CT-guided group(n=59)according to the different guided puncture methods.The diagnostic efficacy and safety of the two guided puncture biopsy methods were analyzed and compared.Results All patients successfully completed the biopsy.The accuracy(the agreement rate between pathological diagnosis and final clinical diagnosis),sensitivity,and complication rate of the 18F-FDG PET/CT-assisted group were 96.30％(52/54),96.15％(50/52),and 3.70％(2/54);and those of the CT-guided group were 84.75％(50/59),83.64％(46/55),and 15.25％(9/59).Ultimately,it was found that the 18F-FDG PET/CT-assisted group performed better in terms of accuracy and complications than CT-guided group,and the differences were statistically significant(x2=4.280 9,P=0.038 5;x2=5.211 4,P=0.022 4).No serious complications such as hemorrhage,abdominal infection,pancreatic fistula,intestinal fistula and so on occurred in all patients.Conclusion 18F-FDG PET/CT image in assisting CT-guided pancreatic tumor puncture possesses more efficient,precise,and safe characteristics,which is the innovation and expansion of traditional CT image-guided puncture biopsy.However,there is still improvement room in terms of economy and feasibility.

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 investigate the clinical value of 18F-FDG PET/CT image in assisting CT-guided puncture of pancreatic tumor.Methods One hundred and thirteen patients with pancreatic tumors were selected and then divided into 18 F-FDG PET/CT image-assisted CT-guided group(abbreviation 18F-FDG PET/CT-assisted group)(n=54)and CT-guided group(n=59)according to the different guided puncture methods.The diagnostic efficacy and safety of the two guided puncture biopsy methods were analyzed and compared.Results All patients successfully completed the biopsy.The accuracy(the agreement rate between pathological diagnosis and final clinical diagnosis),sensitivity,and complication rate of the 18F-FDG PET/CT-assisted group were 96.30％(52/54),96.15％(50/52),and 3.70％(2/54);and those of the CT-guided group were 84.75％(50/59),83.64％(46/55),and 15.25％(9/59).Ultimately,it was found that the 18F-FDG PET/CT-assisted group performed better in terms of accuracy and complications than CT-guided group,and the differences were statistically significant(x2=4.280 9,P=0.038 5;x2=5.211 4,P=0.022 4).No serious complications such as hemorrhage,abdominal infection,pancreatic fistula,intestinal fistula and so on occurred in all patients.Conclusion 18F-FDG PET/CT image in assisting CT-guided pancreatic tumor puncture possesses more efficient,precise,and safe characteristics,which is the innovation and expansion of traditional CT image-guided puncture biopsy.However,there is still improvement room in terms of economy and feasibility.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Different porous structures were studied through finite element analysis and then optimal porous structure was selected for the orthopedic applications.The optimal Voronoi structure was designed and fabricated using 3D printing.The mechanical properties and osseointegration ability were both investigated.The mechanical tests showed that the tensile strength,compressive strength and bending strength of Voronoi structures were obviously higher than that of the human bone,and the modulus of Voronoi structures were similar to human bone.In addition,the animal experimental results exhibited that obvious bone ingrowth was found from Month 1 to Month 6.This study provides some theoretical references for the orthopedic application of porous structures.

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.

Industry-university-research cooperation is not only the core of technological innovation,but also an important way to enhance industrial competitiveness and achieve high-quality development.Industry-university-research cooperation in Liaoning Province has achieved significant results in promoting technological innovation and economic development,but there are still some problems and challenges.The main problems include insufficient depth of industry-university-research cooperation,scattered innovation resources,lack of long-term stable cooperation mechanisms,as well as talent loss and lack of high-quality innovative talents.Through systematically sorting out the existing models of industry-university-research cooperation,it proposes a series of targeted and operable countermeasures and suggestions.These measures and suggestions provide solid theoretical support for the healthy development of industry-university-research cooperation in Liaoning Province.