Objective To investigate the effect of naringenin(Nar)on hippocampal neuronal injury in neonatal mice with bilirubin encephalopathy,focusing on the Nrf2/GPX4-mediated ferroptosis pathway.Methods Neonatal mice were randomly divided into Control group,Model group,Nar low(Nar-L),high dose group(Nar-H)and high dose naringenin combined with Nrf2 inhibitor ML385 group(Nar-H+ML385),with 15 mice in each group.With the exception of the Control group,mice in the other groups were injected with bilirubin solution(20 μg/g)through the cerebellar bulbar cisterna to establish neonatal mouse bilirubin encephalopathy model.After the establishment of the model,intraperitoneal injection of naringin(25 or 100 mg/kg)or ML385(30 mg/kg)was administered once daily for a consecutive period of 7 days.After intervention,the neurobehavioral changes of each group of mice were observed.The water maze experiment was conducted to assess the long-term learning and memory abilities of the mice in each group.Nissl staining was performed to observe hippocampal neuron damage in mice.Chemical methods were used to measure the levels of malondialdehyde(MDA),4-hydroxynonenal(4-HNE),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in the hippocampal tissue of mice.Colorimetric analysis was employed to determine the content of Fe2+in hippocampal tissue.Western blotting was utilized to detect protein expression levels of nuclear associated factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)protein in the hippocampal tissue of mice.Results Compared with the Control group,the Model group showed different degrees of abnormal neural behavior,and the long-term learning and memory ability were significantly reduced(P<0.05),at the same time,the hippocampal nerve was seriously damaged,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly increased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly decreased(P<0.05).Compared with the Model group,the Nar-L and Nar-H groups had less abnormal behavior,and the long-term learning and memory ability were significantly enhanced(P<0.05),at the same time,the hippocampal nerve injury was significantly improved,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly decreased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly increased(P<0.05).However,the combined intervention of ML385 significantly attenuates the beneficial effects of Nar on hippocampal neuron damage in neonatal mice with bilirubin encephalopathy.Conclusion This study suggested that Nar can ameliorate neuronal damage in hippocampus of neonatal mice with bilirubin encephalopathy,possibly through the regulation of iron death mediated by Nrf2/GPX4 axis.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

Early-onset neonatal sepsis (EONS) is a systemic inflammatory response syndrome caused by bacterial and fungal infections within 3 days after birth, which is one of the important causes of poor prognosis and even death in neonates.Early accurate diagnosis and timely treatment are crucial to improving the prognosis and reducing the mortality and unreasonable use of antibiotics.Because umbilical cord blood shares the same cell composition with fetal peripheral blood at the end of pregnancy, and has the advantages of easy availability and painlessness, many researchers have been devoted to exploring umbilical cord blood markers related to the diagnosis of EONS in recent years.Most studies suggest that umbilical cord blood culture, procalcitonin, C-reactive protein and interleukin-6 should be routinely used as single indicators for clinical diagnosis of EONS.The combination of two or more biomarkers may be more accurate for the diagnosis of EONS, which, however, needs to be confirmed with more trials, and it is also a significant direction of future research.In this article, progress in relevant research was reviewed in order to provide reference for early diagnosis of EONS.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

Objective To investigate the effect of naringenin(Nar)on hippocampal neuronal injury in neonatal mice with bilirubin encephalopathy,focusing on the Nrf2/GPX4-mediated ferroptosis pathway.Methods Neonatal mice were randomly divided into Control group,Model group,Nar low(Nar-L),high dose group(Nar-H)and high dose naringenin combined with Nrf2 inhibitor ML385 group(Nar-H+ML385),with 15 mice in each group.With the exception of the Control group,mice in the other groups were injected with bilirubin solution(20 μg/g)through the cerebellar bulbar cisterna to establish neonatal mouse bilirubin encephalopathy model.After the establishment of the model,intraperitoneal injection of naringin(25 or 100 mg/kg)or ML385(30 mg/kg)was administered once daily for a consecutive period of 7 days.After intervention,the neurobehavioral changes of each group of mice were observed.The water maze experiment was conducted to assess the long-term learning and memory abilities of the mice in each group.Nissl staining was performed to observe hippocampal neuron damage in mice.Chemical methods were used to measure the levels of malondialdehyde(MDA),4-hydroxynonenal(4-HNE),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in the hippocampal tissue of mice.Colorimetric analysis was employed to determine the content of Fe2+in hippocampal tissue.Western blotting was utilized to detect protein expression levels of nuclear associated factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)protein in the hippocampal tissue of mice.Results Compared with the Control group,the Model group showed different degrees of abnormal neural behavior,and the long-term learning and memory ability were significantly reduced(P<0.05),at the same time,the hippocampal nerve was seriously damaged,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly increased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly decreased(P<0.05).Compared with the Model group,the Nar-L and Nar-H groups had less abnormal behavior,and the long-term learning and memory ability were significantly enhanced(P<0.05),at the same time,the hippocampal nerve injury was significantly improved,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly decreased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly increased(P<0.05).However,the combined intervention of ML385 significantly attenuates the beneficial effects of Nar on hippocampal neuron damage in neonatal mice with bilirubin encephalopathy.Conclusion This study suggested that Nar can ameliorate neuronal damage in hippocampus of neonatal mice with bilirubin encephalopathy,possibly through the regulation of iron death mediated by Nrf2/GPX4 axis.

Early-onset neonatal sepsis (EONS) is a systemic inflammatory response syndrome caused by bacterial and fungal infections within 3 days after birth, which is one of the important causes of poor prognosis and even death in neonates.Early accurate diagnosis and timely treatment are crucial to improving the prognosis and reducing the mortality and unreasonable use of antibiotics.Because umbilical cord blood shares the same cell composition with fetal peripheral blood at the end of pregnancy, and has the advantages of easy availability and painlessness, many researchers have been devoted to exploring umbilical cord blood markers related to the diagnosis of EONS in recent years.Most studies suggest that umbilical cord blood culture, procalcitonin, C-reactive protein and interleukin-6 should be routinely used as single indicators for clinical diagnosis of EONS.The combination of two or more biomarkers may be more accurate for the diagnosis of EONS, which, however, needs to be confirmed with more trials, and it is also a significant direction of future research.In this article, progress in relevant research was reviewed in order to provide reference for early diagnosis of EONS.

In order to improve the operation difficulties in the narrow space of the nasal maxillary sinus, the nasal continuum minimally invasive surgical robot system is designed. The ball-and-socket joints and NiTiNol tubes are used as the main body of the continuum structure to improve the degree of freedom. The hardware systems and software systems are designed. The security control policies are planned. Finally, the robot confirmed prototype experiments are conducted and the feasibility of continuum robot confirmed through master-slave control experiment and animal experiment.
Animals ; Biomechanical Phenomena ; Equipment Design ; Minimally Invasive Surgical Procedures ; Robotic Surgical Procedures ; Robotics ; Software

Objective:To explore the optimal matching of the current parameters about artificial facial nerve (AFN) for inducing contraction of the orbicularis oris muscle (OOM) in rabbit with peripheral facial paralysis.Methods:According to the combinations of different stimulus parameters, at different time points, we used AFN to induce contraction of the affected side OOM of the paralyzed rabbit in waking state. We recorded the current amplitudes of the threshold stimulation and peak stimulation under each combination, then compared the total charge of the stimulus consumption under different combinations.Results:Compared the total stimulus charge consumption of the AFN threshold stimulation and that in the peak stimulation respectively under different stimulus frequency and pulse width matching combinations, we found that the frequency, the pulse width and the interaction of the frequency and pulse width among different groups could affect the total charge, the differences were statistically significant ( P<0.05). Conclusions:When AFN stimulus frequency is 60 Hz and the stimulus pulse width is 100 μs, the output current intensity is relatively lowest and the total consumed charge is the lowest under the premise of effectively inducing the paralytic side OOM contraction. Thus we recommend this stimulus parametric combination as the optimal combination for meeting the low power consumption of AFN.

Objective: To explore the optimal positions of the implanted stimulating eletrodes for artificial facial nerve (AFN) for inducing contraction of the orbicularis oris muscle (OOM) in rabbit with peripheral facial paralysis. Methods: According to the four microelectrodes of the AFN stimulating side, four modes of the implanted positions were divided. In line with different modes, the electrodes were implanted into the affected OOM of the rabbits with unilateral peripheral facial paralysis. AFN output electric stimulation to induce contraction of the affected OOM with uniform stimulating frequency and pulse length in vitro. Then compared the stimulus threshold amplitude and the peak amplitude separately among different modes by SAS 9.3 version statistical software. Results: The differences of the stimulus threshold amplitude and the peak amplitude had no statistically significant separately between the first mode and the second mode (P>0.05), but there were statistically significant differences between the third mode and the fourth mode (P<0.05). Both kinds of the amplitudes were approximated between the first mode and the second mode respectively, and higher than those in the third mode or the fourth mode. Furthermore, both kinds of the amplitudes in the fourth mode were higher than those in the third mode. Conclusions The microelectrodes of the AFN stimulating lateral are implanted into the upper lip with a public microelectrode and an output microelectrode, into the lower lip with an output microelectrode, and into the way, which is located to the angle 40° to 45° about the line joining between the midpoint of the ipsilateral auricle root and the corner of the mouth with an output microelectrode. This is the third positional mode which requires lowest effective stimulus current intensity. Thus the mode is suitable as the optimal placement programme.

Objectiye To observe the prevalence of prolonged seizures and the changes of biochemical markers of myocardial injury in patients with prolonged seizures after modified electroconvulsive therapy(MECT).Methods Patients treated with MECT or simulated ECT were divided into three groups.Group Ⅰ , 26 patients,experienced at least one prolonged seizure after MECT;group Ⅱ,41 selected patients, had not prolonged seizures at all during a course of MECT treatments and group Ⅲ, 31 patients, received simulated ECT.Biochemical markers of myocardial injury, including phosphocreatine kinase (CK), MR isoenzyme of phosphocreatine kinase (CK-MB), lactate dehydrogenase ( LDH ), α-hydroxybutyrate dehydrogenase ( α-HBDH ) and cardiac troponin (cTnT) ,were measured immediately, 3 hours later and on the following day after the first prolonged seizure for group Ⅰ ,the same time points as group Ⅰ after the first treatment of MECT for group Ⅱ , immediately after simulated ECT for group Ⅲ.These indexes were compared between the patients of three groups.Results The positive rate ofcTnT was 30.8%(8/26) and 17.1% (7/41)in group Ⅰ and Ⅱ respectively, but no difference was found(P＞0.05 ).CK measured immediately after MECT in patients of group Ⅰ was significantly higher than that of group Ⅲ(P ＜ 0.05 ).CK-MB (immediately), LDH ( immediately and 3 hours later) and α-HBDH ( immediately, 3 hours later and on the following day) in patients of group Ⅰ were significantly higher than those of group Ⅱ and Ⅲ measured after MECT or simulated ECT(P＜0.05 ).Conclusion More attention should be paid that absolute or relative hypoxemia may lead to minor myocardial injury.