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FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury
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作者 Mi Zhou Yang-Wu-Yue Liu +11 位作者 Yu-Hang He Jing-Yu Zhang Hao Guo Hao Wang Jia-Kui Ren Yi-Xun Su Teng Yang Jia-Bo Li Wen-Hui He Peng-Jiao Ma Man-Tian Mi Shuang-Shuang Dai 《Military Medical Research》 SCIE CAS CSCD 2024年第4期521-542,共22页
Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulatio... Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI. 展开更多
关键词 Traumatic brain injury(TBI) NEUTROPHIL Forkhead box protein O1(FOXO1) acute stage Chronic stage
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Effect of Acupuncture Combined with Blood-letting by a Three-edged Needle on 50 cases of Bell's Palsy at the Acute Stage 被引量:7
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作者 赵吉平 朴彦政 +1 位作者 王军 陈正秋 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2010年第2期118-121,共4页
Objective:To observe clinical effects of acupuncture combined with blood-letting by a three-edged needle for treating Bell's palsy of wind-heat syndrome at the acute stage.Methods:One hundred patients were randoml... Objective:To observe clinical effects of acupuncture combined with blood-letting by a three-edged needle for treating Bell's palsy of wind-heat syndrome at the acute stage.Methods:One hundred patients were randomly divided into a treatment group(50 cases) treated by acupuncture plus blood-letting and a control group(50 cases) treated by simple acupuncture.Four courses of treatments were given in both groups.The main symptoms and signs were observed and clinical effects evaluated with scores after one week,2 weeks and one month of treatments respectively.Results:After treatment,the scores for symptoms and signs were significantly different from those before treatment in both groups(P<0.05 or P<0.01).After one month of treatment,the improvement of the symptoms and signs in the treatment group was more than that in the control group with a significant difference(P<0.05).Conclusion:Acupuncture plus blood-letting can produce good therapeutic effects on Bell's palsy of wind-heat syndrome at the acute stage. 展开更多
关键词 ACUPUNCTURE blood-letting with a three-edged needle acute stage of Bell's Palsy
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Effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia
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作者 Yi-Kun Sun Li-Jun Wu +5 位作者 Yuan-Yuan Li Hao-Qi Liu Na An Ke Song Hua Zhang Yong-Hong Gao 《Journal of Hainan Medical University》 2021年第23期1-7,共7页
Objective:To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia.Methods:The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion,MCAO)... Objective:To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia.Methods:The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion,MCAO)was established by suture occlusion.Except the sham operation group,the other groups were randomly divided into model group and Xingnaojing group.The rats in Xingnaojing group were intraperitoneally injected with Xingnaojing injectionaccording to 0.18ml/100g,and the sham operation group and model group were given the same amount of normal saline respectively.24 hours after the establishment of the model,the morphological changes of neurons in the penumbra of the rats were observed by Nissl staining,the ultrastructural changes of neurovascular unit(Neurovascular unit,NVU)were observed by transmission electron microscope(Transmission electron microscope,TEM),and the apoptosis of the ischemic penumbra was detected by in situ apoptosis(TdT-mediated Dutp Nick-End Labeling,TUNEL).Magnetic resonance imaging was used to observe the ischemic evolution of the penumbra of the same rat at 4.5 h and 24 h,respectively.Results:Compared with the sham operation group,the number of neurons in the model group was significantly reduced,the structure of Nissl corpuscles was destroyed,the outline was blurred or disappeared,the pathological morphology of NVU ultrastructure was obviously damaged under transmission electron microscope,a large number of apoptotic cells could be seen in the model group by TUNEL staining(P<0.01),and magnetic resonance imaging showed that there was a large area infarction in the brain tissue of the model group.Compared with the model group,the pathomorphology of neurons and NVU ultrastructure in Xingnaojing group was significantly improved,the number of apoptotic cells was significantly decreased(P<0.01),and the loss rate of penumbra was significantly lower in Xingnaojing group(P<0.05).Conclusion:Xingnaojing injection can improve the state of neurons in ischemic penumbra,reduce the injury of glial cells and microvessels,inhibit apoptosis,promote the transformation of penumbra in rats with acute cerebral ischemia,and save part of penumbra to some extent.it has a certain protective effect on the brain tissue of penumbra in the acute stage of cerebral ischemia. 展开更多
关键词 Xingnaojing injection acute stage of cerebral ischemia PENUMBRA NEURON MRI
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Fluid therapy for severe acute pancreatitis in acute response stage 被引量:92
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作者 MAO En-qiang TANG Yao-qing FEI Jian QIN Shuai WU Jun LI Lei MIN Dong ZHANG Sheng-dao 《Chinese Medical Journal》 SCIE CAS CSCD 2009年第2期169-173,共5页
Background Fluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for... Background Fluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP. Methods Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n=36) and a controlled fluid expansion group (Group II n=-40). Hemodynamic disorders were either quickly (fluid infusion rate was 10-15 ml.kg-1-h-1, Group I) or gradually improved (fluid infusion rate was 5-10 ml-kg1.h-1, Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained. Results The two groups had statistically different (P 〈0.05) time intervals to meet fluid expansion criteria (Group I, 13.5±6.6 hours; Group II, (24.0±5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P 〈0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6%±6.8%) than in Group II (38.5%±5.4%) (P〈0.01). Amount of crystalloid and colloid in group I ((4028±1980)ml and (1336±816)ml) on admission day was more than those of group II ((2472±1871)ml and (970±633)ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P〉0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378±2751)ml) than in Group II ((4215±1998)ml, P 〈0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P〈0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P〈0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P 〈0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P〈0.05). Conclusions Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset. Chin Med J 2009; 122(2): 169-173 展开更多
关键词 pancreatitis acute necrotizing RESUSCITATION acute response stage
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Acupuncture and moxibustion combined with western medication for ninety cases of Bell’s palsy at different stages: A randomized controlled trial 被引量:2
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作者 Hui-fang Mao Wei Huang +3 位作者 De-guang Ding Min Yao Ting Zhang Bei Xiao 《World Journal of Acupuncture-Moxibustion》 CSCD 2019年第4期249-253,共5页
Objective:To observe the differences in the clinical effect on Bell’s palsy at the acute stage and the recover stage,as well as the differences in the clinical effect between the simple acupuncture-moxibustion therap... Objective:To observe the differences in the clinical effect on Bell’s palsy at the acute stage and the recover stage,as well as the differences in the clinical effect between the simple acupuncture-moxibustion therapy and the combined therapy of acupuncture-moxibustion and western medication,explore the optimal intervention time point and therapeutic regimen.Methods:All of the patients were collected from the outpatients and the inpatients in the Specific Department of Acupuncture for Facial Paralysis in Hubei Chinese Medicine Hospital.A total of 128 patients with Bell’s palsy were collected from February 2017 through to February 2018 and 90 patients of them were in compliance with the inclusion criteria.90 cases were randomized into three groups,named group A(acupuncture and moxibustion at the acute stage),group B(acupuncture and moxibustion combined with western medication at the acute stage)and group C(acupuncture and moxibustion combined with western medication at the recovery stage),30 cases in each one.In the group A,acupuncture and moxibustion were adopted at the acute stage of Bell’s palsy.In the group B,at the acute stage,acupuncture and moxibustion were adopted in combination with the oral medication of hormone and vitamin.In the group C,at the recovery stage,acupuncture and moxibustion were adopted in combination with the oral medication of hormone and vitamin.The clinical healing time and the total effective rate were observed in the patients of the three groups and the occurrence of sequelae in facial paralysis was followed-up.Result:①The clinical healing time in the Group B was slightly shorter than the Group A,but without statistical significance in comparison(P>0.05).The clinical healing time in either the Group A or the Group B was shorter than Group C,indicating the statistical significance in comparison(both P<0.05).②The results of 3-month follow-up observation showed that there were 3 cases of sequelae in the group A,2 cases in the Group B and 7 cases in the Group C.③After treatment,the total effective rate in either the Group A or the Group B was higher than the Group C,indicating the statistical significance in comparison(both P<0.05).Conclusion:The simple use of acupuncture and moxibustion at the acute stage achieves the similar clinical effect on Bell’s palsy as the treatment of acupuncture-moxibustion combined with western medication.The simple application of acupuncture and moxibustion prevents from the potential side effects of hormone to the largest extent and displays its dominate advantages in safety.Besides,the early intervention of acupuncture-moxibustion shortens the healing time and effectively improves the prognosis of Bell’s palsy. 展开更多
关键词 ACUPUNCTURE-MOXIBUSTION Bell’s palsy acute stage Recovery stage Hormonotherapy VITAMIN
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