Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergi...Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 days） post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.展开更多
Cold-inducible RNA-binding protein（CIRP）, a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5℃ on t...Cold-inducible RNA-binding protein（CIRP）, a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5℃ on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP m RNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo f...Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo further surgical treatment.Dexamethasone has anti-inflammatory and immunomodulatory effects,and low dosages are safe and effective for the treatment of many diseases,such as ankylosing spondylitis and community-acquired pneumonia.However,the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood.Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group.Atorvastatin,dexamethasone,or their combination was added to the culture medium.The main results were as follows:hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1μM atorvastatin and 0.1μM dexamethasone.Atorvastatin,dexamethasone,or their combination could markedly improve the recovery of injured endothelial cells.Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin,dexamethasone,or their combination exhibited varying levels of rescue of endothelial cell function.Hopping probe ion conductance microscopy,western blot assay,and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin,dexamethasone,or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid.Moreover,the curative effect of the combined treatment was significantly better than that of either single treatment.Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased,as was expression of the tight junction protein and vascular permeability marker vascular endothelial cadherin in each treatment group compared with the hematoma stimulation group.Hematoma fluid in patients with chronic subdural hematoma may damage vascular endothelial cells.However,atorvastatin combined with low-dose dexamethasone could rescue endothelial cell dysfunction by increasing the expression of tight junction proteins after hematoma injury.The effect of combining atorvastatin with low-dose dexamethasone was better than that of atorvastatin alone.Increased expression of Krüppel-like factor 2 may play an important role in the treatment of chronic subdural hematoma.The animal protocols were approved by the Animal Care and Use Committee of Tianjin Medical University of China on July 31,2016(approval No.IRB2016-YX-036).The study regarding human hematoma samples was approved by the Ethics Committee of Tianjin Medical University of China on July 31,2018(approval No.IRB2018-088-01).展开更多
Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor c...Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.展开更多
Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulo...Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.展开更多
A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this...A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats（cold water swimming for 3 minutes at 4℃） spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~＋ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.展开更多
Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumati...Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.Hypotension,brain-injury severity,and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency.These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis.The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury,especially those with hypotension,hemorrhagic cerebral contusions,diffuse axonal injury,and brain herniation.Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency.This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University,China in December 2011(approval No.201189).展开更多
BACKGROUND A significant relationship between gastric cancer(GC)and depression has been found in the last 20 years.However,there is no comprehensive information that helps researchers find popular and potential resear...BACKGROUND A significant relationship between gastric cancer(GC)and depression has been found in the last 20 years.However,there is no comprehensive information that helps researchers find popular and potential research directions on GC and depression.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between GC and depression.METHODS We used the Web of Science Core Collection to search and collate the literature on GC and depression from 2000 to 2022 on 31 May,2023.Then,visualization analysis was performed using VOSviewer software(version 1.6.19)and the Bibliometrix package in R software.RESULTS We retrieved 153 pertinent publications from 2000 to 2022.The annual publication count showed an overall upward trend.China had the most prominent publications and significant contributions to this field(n=64,41.83%).Before 2020,most studies focused on“the effect of GC on the development and progression of depression in patients.”The latest research trends indicate that“the effect of depression on the occurrence and development of GC and its mechanism”will receive more attention in the future.CONCLUSION The study of“the effect of depression on the occurrence and development of GC and its mechanism”has emerged as a novel research theme over the past two years,which may become a research hotspot in this field.This study provides new insights into the hotpots and frontiers of the relationship between GC and depression,potentially guiding researchers toward hot research topics in the future.展开更多
Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal ex...Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.展开更多
Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of...Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.展开更多
Background： Traumatic brain injury （TBI） is a life-threatening disease worldwide. Regulatory T cells （Treg ceils） were involved in the immunological system in central nervous system. It is defined as a subpopulat...Background： Traumatic brain injury （TBI） is a life-threatening disease worldwide. Regulatory T cells （Treg ceils） were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4＋ cells that express CD25 and transcription lactor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI. Methods： A clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University （Tianjin, China）. Forty patients and 30 healthy controls were recruited t＇rom August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1,4, 7, 14, and 21 days alter TBI. Blood sample （ 1 ml） was withdrawn in the morning and processed within 2 h. Results： There was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1st day after TBI. Treg level was decreased on the 4th day, climbed tip on the 7th day and peaked on 14th day after TBI. Treg cells declined to the normal level on 21th day alter TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4＋ inononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 mononuclear cells in the first 14 days. Conclusions： The level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.展开更多
INTRODUCTIONMicroneurosurgery made its debut in the early 1960s. It became popular in the medical field and became a primary operation method in neurosurgery since it improved the efficacy of neurosurgery with a less ...INTRODUCTIONMicroneurosurgery made its debut in the early 1960s. It became popular in the medical field and became a primary operation method in neurosurgery since it improved the efficacy of neurosurgery with a less surgery-related injury. Over the past five decades, the accumulation of experience of microsurgery, improvement of microsurgery techniques, refined micro-instruments, and advanced preoperative diagnostic imaging allowed the evolution of microneurosurgery techniques and further reduced surgery-related trauma.展开更多
Despite major advances achieved in percutaneous coronary intervention(PCI)and antithrombotic therapies,in-stent restenosis(ISR)is still a challenging clinical problem after PCI.It is very important to identify a new p...Despite major advances achieved in percutaneous coronary intervention(PCI)and antithrombotic therapies,in-stent restenosis(ISR)is still a challenging clinical problem after PCI.It is very important to identify a new parameter for ISR risk stratification and as potential pharmacological targets.We previously reviewed that Neutrophil-to-lymphocyte ratio(NLR)may be the best predictor of ISR among several parameters of blood cells.Type 2 diabetes mellitus(T2DM)is closely related to inflammation and acts as an independent risk factor of ISR.However,few studies have evaluated the predictive role of the dynamic changes of NLR on ISR in patients with T2DM.Therefore,we aimed to analyze preprocedural NLR value in the first PCI and the second coronary angiography(CAG),and evaluate its predictive value on ISR in patients with T2DM.展开更多
Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical micr...Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope.The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma(VS),as an alternative to a binocular surgical microscope.Methods::Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018.The demographics and tumor characteristics(size,Koos grade,composition[cystic or solid mass])were matched between the two groups of patients.The following outcome measurements were compared between the two groups:duration of surgery,volume of blood loss,extent of tumor resection,number of operating field adjustments,pre-and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery,complications and surgeons’comfortability.Results::A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope(cases,n=39)or a surgical microscope(control,n=42).Patients in the two groups had comparable tumor location(P=0.439),Koos grading(P=0.867),and composition(P=0.891).While no significant differences in the duration of surgery(P=0.172),extent of tumor resection(P=0.858),facial function(P=0.838),and hearing ability(P=1.000),patients operated on under an exoscope had less blood loss(P=0.036)and a fewer field adjustments(P<0.001).Both primary and assistant surgeons reported a high level of comfort operating under the exoscope(P=0.001 and P<0.001,respectively).Conclusions::The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs,as compared to a surgical microscope.After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax,the exoscope system provided a comfortable,high-resolution visualization without compromising operational efficiency and patient safety.展开更多
基金supported by the National Natural Science Foundation of China,No.81330029,81671380the Natural Science Foundation of Tianjin City of China,No.17JCZDJC35900
文摘Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 days） post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.
基金supported by the National Natural Science Foundation of China,No.81303091
文摘Cold-inducible RNA-binding protein（CIRP）, a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5℃ on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP m RNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
基金supported by the National Natural Science Foundation of China,Nos.81671380(to DW),81720108015(to JNZ),81930031(to JNZ),81771221(to YL),and 81901525(to SZ)the Clinical Study of Tianjin Medical University of China,No.2017kylc007(to RCJ)+1 种基金the Natural Science Foundation of Tianjin of China,No.17JCZDJC35900(to DW)the Tianjin Science and Technology Plan Program of China,No.19YFZCSY00650(to RCJ)。
文摘Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo further surgical treatment.Dexamethasone has anti-inflammatory and immunomodulatory effects,and low dosages are safe and effective for the treatment of many diseases,such as ankylosing spondylitis and community-acquired pneumonia.However,the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood.Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group.Atorvastatin,dexamethasone,or their combination was added to the culture medium.The main results were as follows:hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1μM atorvastatin and 0.1μM dexamethasone.Atorvastatin,dexamethasone,or their combination could markedly improve the recovery of injured endothelial cells.Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin,dexamethasone,or their combination exhibited varying levels of rescue of endothelial cell function.Hopping probe ion conductance microscopy,western blot assay,and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin,dexamethasone,or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid.Moreover,the curative effect of the combined treatment was significantly better than that of either single treatment.Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased,as was expression of the tight junction protein and vascular permeability marker vascular endothelial cadherin in each treatment group compared with the hematoma stimulation group.Hematoma fluid in patients with chronic subdural hematoma may damage vascular endothelial cells.However,atorvastatin combined with low-dose dexamethasone could rescue endothelial cell dysfunction by increasing the expression of tight junction proteins after hematoma injury.The effect of combining atorvastatin with low-dose dexamethasone was better than that of atorvastatin alone.Increased expression of Krüppel-like factor 2 may play an important role in the treatment of chronic subdural hematoma.The animal protocols were approved by the Animal Care and Use Committee of Tianjin Medical University of China on July 31,2016(approval No.IRB2016-YX-036).The study regarding human hematoma samples was approved by the Ethics Committee of Tianjin Medical University of China on July 31,2018(approval No.IRB2018-088-01).
基金supported by the National Natural Science Foundation of China,No.30772229(to JNZ),No.81200907(to HJW)the Natural Science Foundation of Tianjin of China,No.12JCQNJC06800(to HJW)+1 种基金the Science and Technology Projects in Key Areas of Traditional Chinese Medicine of Tianjin of China,No.2018001(to ZGW)the Scientific Research Program Project of Tianjin Education Commission of China,No.2018ZD03(to ZGW)
文摘Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.
基金supported by the National Natural Science Foundation of China,No.81330029(to JNZ),81501057(to YT)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education in China,No.2016YD02(to YW)the Technology Program Fund of Tianjin Health and Family Planning Commission for the Key Field of Traditional Chinese Medicine,No.2018001(to ZGW)
文摘Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.
基金supported by a grant from the Incubation Project of Natural Science Foundation of Tianjin Medical University General Hospital in China,No.303071901401the Natural Science Foundation of Tianjin of China,No.13JCZDJC30800the National Natural Science Foundation of China,No.81271361 and 81330029
文摘A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats（cold water swimming for 3 minutes at 4℃） spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~＋ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.81671902(to XC)81501704(to YC)+3 种基金the Project of Tianjin Applied Basic and Cutting-edge Technological Research of China,No.17JCYBJC25200(to XC)15JCQNJC44900(to YC)Tianjin Health Care Elite Prominent Young Doctor Development Program(to XC)the Young and Middle-aged Backbone Innovative Talent Program(to XC)
文摘Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.Hypotension,brain-injury severity,and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency.These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis.The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury,especially those with hypotension,hemorrhagic cerebral contusions,diffuse axonal injury,and brain herniation.Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency.This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University,China in December 2011(approval No.201189).
文摘BACKGROUND A significant relationship between gastric cancer(GC)and depression has been found in the last 20 years.However,there is no comprehensive information that helps researchers find popular and potential research directions on GC and depression.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between GC and depression.METHODS We used the Web of Science Core Collection to search and collate the literature on GC and depression from 2000 to 2022 on 31 May,2023.Then,visualization analysis was performed using VOSviewer software(version 1.6.19)and the Bibliometrix package in R software.RESULTS We retrieved 153 pertinent publications from 2000 to 2022.The annual publication count showed an overall upward trend.China had the most prominent publications and significant contributions to this field(n=64,41.83%).Before 2020,most studies focused on“the effect of GC on the development and progression of depression in patients.”The latest research trends indicate that“the effect of depression on the occurrence and development of GC and its mechanism”will receive more attention in the future.CONCLUSION The study of“the effect of depression on the occurrence and development of GC and its mechanism”has emerged as a novel research theme over the past two years,which may become a research hotspot in this field.This study provides new insights into the hotpots and frontiers of the relationship between GC and depression,potentially guiding researchers toward hot research topics in the future.
基金supported by the National Natural Science Foundation of China,No.81330029,81501057the Natural Science Foundation of Tianjin of China,No.17JCQNJC12000the Tianjin Medical University General Hospital Funding in China,No.ZYYFY2016014
文摘Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.
基金supported by a grant from the International S cience and Technology Cooperation Projects of China,No.2011DFG33430
文摘Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.
文摘Background： Traumatic brain injury （TBI） is a life-threatening disease worldwide. Regulatory T cells （Treg ceils） were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4＋ cells that express CD25 and transcription lactor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI. Methods： A clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University （Tianjin, China）. Forty patients and 30 healthy controls were recruited t＇rom August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1,4, 7, 14, and 21 days alter TBI. Blood sample （ 1 ml） was withdrawn in the morning and processed within 2 h. Results： There was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1st day after TBI. Treg level was decreased on the 4th day, climbed tip on the 7th day and peaked on 14th day after TBI. Treg cells declined to the normal level on 21th day alter TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4＋ inononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 mononuclear cells in the first 14 days. Conclusions： The level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.
文摘INTRODUCTIONMicroneurosurgery made its debut in the early 1960s. It became popular in the medical field and became a primary operation method in neurosurgery since it improved the efficacy of neurosurgery with a less surgery-related injury. Over the past five decades, the accumulation of experience of microsurgery, improvement of microsurgery techniques, refined micro-instruments, and advanced preoperative diagnostic imaging allowed the evolution of microneurosurgery techniques and further reduced surgery-related trauma.
文摘Despite major advances achieved in percutaneous coronary intervention(PCI)and antithrombotic therapies,in-stent restenosis(ISR)is still a challenging clinical problem after PCI.It is very important to identify a new parameter for ISR risk stratification and as potential pharmacological targets.We previously reviewed that Neutrophil-to-lymphocyte ratio(NLR)may be the best predictor of ISR among several parameters of blood cells.Type 2 diabetes mellitus(T2DM)is closely related to inflammation and acts as an independent risk factor of ISR.However,few studies have evaluated the predictive role of the dynamic changes of NLR on ISR in patients with T2DM.Therefore,we aimed to analyze preprocedural NLR value in the first PCI and the second coronary angiography(CAG),and evaluate its predictive value on ISR in patients with T2DM.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81671902)the Project of Tianjin Applied Basic and Cutting-edge Technological Research(No.17JCYBJC25200)by the Tianjin Health Care Elite Prominent Young Doctor Development Program and Young,and middle-aged innovative talent training program.
文摘Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope.The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma(VS),as an alternative to a binocular surgical microscope.Methods::Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018.The demographics and tumor characteristics(size,Koos grade,composition[cystic or solid mass])were matched between the two groups of patients.The following outcome measurements were compared between the two groups:duration of surgery,volume of blood loss,extent of tumor resection,number of operating field adjustments,pre-and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery,complications and surgeons’comfortability.Results::A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope(cases,n=39)or a surgical microscope(control,n=42).Patients in the two groups had comparable tumor location(P=0.439),Koos grading(P=0.867),and composition(P=0.891).While no significant differences in the duration of surgery(P=0.172),extent of tumor resection(P=0.858),facial function(P=0.838),and hearing ability(P=1.000),patients operated on under an exoscope had less blood loss(P=0.036)and a fewer field adjustments(P<0.001).Both primary and assistant surgeons reported a high level of comfort operating under the exoscope(P=0.001 and P<0.001,respectively).Conclusions::The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs,as compared to a surgical microscope.After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax,the exoscope system provided a comfortable,high-resolution visualization without compromising operational efficiency and patient safety.
