ABSTRACT
BACKGROUND: Carcinoma of unknown primary (CUP) with a gastrointestinal profile is categorized by the European Society of Medical Oncology (ESMO) guidelines into favorable and unfavorable subsets. Favorable CUPs benefit from site-specific chemotherapy (CT), while the optimal treatment for unfavorable CUPs is still undefined. MATERIALS AND METHODS: We conducted a single-center retrospective study to describe outcomes of patients with CUP with a gastrointestinal profile referred to our center from January 2000 to August 2023. Favorable CUPs were defined as CK7-/CK20+/CDX2+ by immunohistochemistry, according to the ESMO definition; all other cases were considered unfavorable. The main endpoint was the progression-free survival (PFS) of first-line CT for advanced disease in all patients and in the unfavorable group. RESULTS: A total of 56 patients were included, of whom 46 (82%) had unfavorable CUPs. After a median follow-up of 43.9 months, the median overall survival (mOS) was 11.8 months [95% confidence interval (CI) 8.3-15.3 months]. At univariate analysis, the presence of peritoneal metastases and residual tumor after primary surgery were associated with a shorter OS. The median PFS (mPFS) was 6.1 months (95% CI 3.6-8.7 months). In the unfavorable CUP subgroup, the mOS was 12.6 months (95% CI 8.7-16.5 months), the mPFS was 6.1 months (95% CI 3.5-8.9 months) and none of the CT regimens used showed to portend better PFS. The most relevant altered genes included: KRAS (9/29; 31%), BRAF (1/26; 4%), NRAS (1/25; 4%), TP53 (9/23; 39%). CONCLUSIONS: CUPs with a gastrointestinal profile are characterized by poor prognosis and the absence of biomarker for treatment personalization. No CT regimen was superior in terms of PFS in patients with unfavorable CUPs.
ABSTRACT
BACKGROUND: The aim of this study was to determine the relationship between apolipoprotein E (ApoE)-ε4 genotype and senile dementia (SD) by analyzing the ApoE allelic frequency distributions among the elderly Han Chinese population. METHODS: For this purpose, a total of 316 Chongqing residents aged ≥60 years were classified as SD or control groups following the criteria of National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. Genomic DNA was isolated from the peripheral blood lymphocytes and exon 4 of the ApoE gene with polymorphism sites was amplified by PCR and genotypes determined by restriction fragment length polymorphism (RFLP). RESULTS: We found that the most prevalent genotype was ApoE-ε3/3, followed in order by ApoE-ε3/4 and ApoE-ε2/2. The estimated ApoE allelic frequencies in individuals with SD were 0.095, 0.560, and 0.345 for ε2, ε3, and ε4, respectively. In controls, the corresponding ApoE allelic frequencies were 0.146, 0.699, and 0.155. The percentage of ε4 allele carriers in SD group was significantly higher than that in control group (P<0.01); while those of ε2 and ε3 genotypes were lower in SD group as compared with control group. CONCLUSIONS: We concluded that in the elderly Han Chinese residents of Chongqing aged 60 years and over, ApoE-ε3/3 and ApoE-ε2/2 were the most and least prevalent genotypes, respectively. Further, based on strong linkage, ApoEε4 allele might be a significant risk factor for the development of senile dementia.
Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Aged , Aged, 80 and over , Asian People/genetics , Female , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Middle AgedABSTRACT
We present precision Penning trap mass measurements of neutron-rich calcium and potassium isotopes in the vicinity of neutron number N=32. Using the TITAN system, the mass of 51K was measured for the first time, and the precision of the (51,52)Ca mass values were improved significantly. The new mass values show a dramatic increase of the binding energy compared to those reported in the atomic mass evaluation. In particular, 52Ca is more bound by 1.74 MeV, and the behavior with neutron number deviates substantially from the tabulated values. An increased binding was predicted recently based on calculations that include three-nucleon (3N) forces. We present a comparison to improved calculations, which agree remarkably with the evolution of masses with neutron number, making neutron-rich calcium isotopes an exciting region to probe 3N forces.
ABSTRACT
TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN) constitutes the only high precision mass measurement setup coupled to a rare isotope facility capable of increasing the charge state of short-lived nuclides prior to the actual mass determination in a Penning trap. Recent developments around TITAN's charge breeder, the electron beam ion trap, form the basis for several successful experiments on radioactive isotopes with half-lives as low as 65 ms and in charge states as high as 22+.
ABSTRACT
Collinear-laser spectroscopy with the bunched-beams technique was used for the study of neutron deficient Rb isotopes, out to (74)Rb (N = Z = 37) at TRIUMF. The measured hyperfine coupling constants of (76,78m)Rb were in agreement with literature values. The nuclear spin of (75)Rb was confirmed to be I = 3/2, and its hyperfine coupling constants were measured for the first time. The mean-square charge radius of (74)Rb was determined for the first time. This result has improved the isospin symmetry breaking correction term used to calculate the Ft value, with implications for tests of the unitarity of the Cabibbo-Kobayashi-Maskawa matrix.
ABSTRACT
In-source resonant ionization laser spectroscopy of the even-A polonium isotopes (192-210,216,218)Po has been performed using the 6p(3)7s (5)S(2) to 6p(3)7p (5)P(2) (λ=843.38 nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in (200-210)Po with a previous data set allows us to test for the first time recent large-scale atomic calculations that are essential to extract the changes in the mean-square charge radius of the atomic nucleus. When going to lighter masses, a surprisingly large and early departure from sphericity is observed, which is only partly reproduced by beyond mean field calculations.
ABSTRACT
Penning trap mass measurements of short-lived nuclides have been performed for the first time with highly charged ions, using the TITAN facility at TRIUMF. Compared to singly charged ions, this provides an improvement in experimental precision that scales with the charge state q. Neutron-deficient Rb isotopes have been charge bred in an electron beam ion trap to q=8-12+ prior to injection into the Penning trap. In combination with the Ramsey excitation scheme, this unique setup creating low energy, highly charged ions at a radioactive beam facility opens the door to unrivaled precision with gains of 1-2 orders of magnitude. The method is particularly suited for short-lived nuclides such as the superallowed ß emitter 74Rb (T(1/2)=65 ms). The determination of its atomic mass and an improved Q(EC) value are presented.
ABSTRACT
Collinear laser spectroscopy was performed on Ga (Z=31) isotopes at ISOLDE, CERN. A gas-filled linear Paul trap (ISCOOL) was used to extend measurements towards very neutron-rich isotopes (N=36-50). A ground state (g.s.) spin I=1/2 is measured for 73Ga, being near degenerate with a 3/2{-} isomer (75 eVâ²E{ex}â²1 keV). The 79Ga g.s., with I=3/2, is dominated by protons in the πf{5/2} orbital and in 81Ga the 5/2{-} level becomes the g.s. The data are compared to shell-model calculations in the f{5/2}pg{9/2} model space, calling for further theoretical developments and new experiments.
ABSTRACT
We report the first confirmation of the predicted inversion between the pi2p3/2 and pi1f5/2 nuclear states in the nu(g)9/2 midshell. This was achieved at the ISOLDE facility, by using a combination of in-source laser spectroscopy and collinear laser spectroscopy on the ground states of 71,73,75Cu, which measured the nuclear spin and magnetic moments. The obtained values are mu(71Cu)=+2.2747(8)mu(N), mu(73Cu)=+1.7426(8)mu(N), and mu(75Cu)=+1.0062(13)mu(N) corresponding to spins I=3/2 for 71,73Cu and I=5/2 for 75Cu. The results are in fair agreement with large-scale shell-model calculations.
ABSTRACT
A new type of fluorous distannoxanes, [XRf2SnOSnRf2Y]2 (Rf = C6F13C2H4; X, Y = C6F13SO3 (2) and (C6F13SO2)2N, Cl (3)) was prepared successfully as hydrates from the reaction of [ClRf2SnOSnRf2Cl]2 with C6F13SO3Ag and (C6F13SO2)2NAg, respectively. Despite their high fluorine content (59.85 and 59.27% F), these distannoxanes were completely insoluble in fluorocarbons as well as hydrocarbons and halo alkanes. In contrast to this, fluorous distannoxanes 2 and 3 were soluble in polar organic solvents, such as EtOAc, acetone, and THF. When 2 and 3 were added to a two-phase mixture of fluorocarbon and EtOAc, the mixture turned miscible in proportion to the amount of 2 and 3 added, and finally, the mixture turned to a homogeneous solution.
ABSTRACT
BACKGROUND: This report focused on investigating the relationship between alcohol consumption and dementia in elderly people through prospective studies. METHODS: We conducted a 2-year follow-up study of elderly people from six communities in Chongqing, China. Dementia was detected using the Mini-Mental State Examination (MMSE) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). The relationship between alcohol consumption and dementia was investigated using multiple logistic regression models, adjusting for the potential confounders age, sex, educational level and cigarette smoking. RESULTS: Light-to-moderate drinking was associated with a significantly lower risk of dementia compared with non-drinking. Excessive drinking was related to a higher risk of dementia. The effect of light-to-moderate drinking seemed most prominent among vascular dementia, 0.63 (0.55-0.72) for Alzheimer's disease, 0.31 (0.19-0.51) for vascular dementia and 0.45 (0.12-1.69) for other dementia. In a model adjusting for confounding variables, a light-to-moderate intake of beer was associated with a significantly higher risk of dementia than a non-drinker of beer. For wine, a significantly lower risk of dementia existed for a light-to-moderate drinker. CONCLUSIONS: Light-to-moderate drinking was associated with a significantly lower risk of dementia compared with a non-drinker.
Subject(s)
Alcohol Drinking/epidemiology , Dementia/epidemiology , Aged , China/epidemiology , Dementia/classification , Dementia/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neuropsychological Tests , Prevalence , Risk Factors , Severity of Illness IndexABSTRACT
The reactions of 1,3-dichloro-1,1,3,3-tetrabutyldistannoxane and dialkyltin dihalides with silver perfluorooctanesulfonate provided the corresponding sulfonates as hydrates. The number of water molecules (n) of hydration was dependent on the conditions. The distannoxane derivative was identified as n from 0.5 to 6, while in the hydrated mononuclear species and DMSO complexes n varied widely from 4 to 13. 119Sn NMR spectroscopy and conductivity measurements indicated the ionic dissociation of these compounds in solution. These compounds exhibited unusually high solubility in polar organic solvents. The ionic dissociation together with facile hydration probably causes the unusual solubility. The Lewis acidity of these compounds was found to be high among organotin derivatives on the basis of ESR spectra of superoxide/metal-ion complexes. In contrast to well-known organotin triflates, these compounds suffered no hydrolysis upon storage in open air. The high catalytic activity of the distannoxane 1 was exemplified for various carbon-carbon bond-forming reactions, such as Mukaiyama-aldol as well as -Michael reactions and allylation of aldehydes.
ABSTRACT
BACKGROUND: Adhesion molecules play important roles in the pathophysiology of ischemic stroke. The aim of the present study was to investigate whether serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cellular adhesion molecule 1 (sVCAM-1) and soluble E-selectin were associated with neurological deterioration of ischemic stroke. METHODS: 238 consecutive patients with ischemic stroke examined within 24 h from onset were enrolled into the study. The stroke severity was daily assessed with the NIH Stroke Scale (NIHSS) within the first week after admission. Serum levels of sICAM-1, sVCAM-1 and sE-selectin after admission were measured using enzyme-linked immunosorbent assay. Multivariate logistic regression was used to analyze the association of serum levels of sICAM-1, sVCAM-1 and sE-selectin on admission with the neurological deterioration of ischemic stroke, adjusted for potential confounders. RESULTS: 52 (21.8%) out of 238 stroke patients suffered from neurological deterioration. Serum levels of sICAM-1 on admission of stroke patients were significantly higher than those of healthy controls. Compared with patients without deterioration, patients with neurological deterioration had higher levels of sICAM-1, but not of sVCAM-1 and sE-selectin. On multivariate logistic regression, the serum level of sICAM-1 on admission was associated with neurological deterioration of stroke (OR 2.92, 95% CI 1.41-6.05). Other variables associated with neurological deterioration were fasting serum glucose (OR 1.65, 95% CI 1.24-2.20), baseline fibrinogen (OR 1.31, 95% CI 1.13-1.52) and NIHSS score (OR 1.23, 95% CI 1.15-1.32). CONCLUSIONS: The serum level of sICAM-1 on admission is associated with neurological deterioration of ischemic stroke.
Subject(s)
Brain Ischemia/blood , E-Selectin/blood , Intercellular Adhesion Molecule-1/blood , Stroke/blood , Vascular Cell Adhesion Molecule-1/blood , Aged , Aged, 80 and over , Brain Ischemia/complications , Brain Ischemia/therapy , Case-Control Studies , China , Cohort Studies , Female , Hospitalization , Humans , Male , Middle Aged , Severity of Illness Index , Stroke/etiology , Stroke/therapy , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the role of the thrombin in inducing inflammatory response in brain tissue adjacent to hematoma in the brain. METHODS: Seventy-two male Wistar rats were randomly divided into two groups: sham-operated control group and thrombin injection group. Immunohistochemical technique and myeloperoxidase (MPO) determination were respectively used to evaluate intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration in adjacent brain tissue of the thrombin injection zone at 6, 12, 24, 48, 72 and 128 hours after thrombin injection. RESULTS: The expression of ICAM-1 in tissues adjacent to thrombin injection started to increase 6 hours after the injection, peaking at 72 hours, and lasting for 120 hours. MPO activity of tissues in the area increased 6 hours, reached a high level at 24 hours, then decreased slightly, and it peaked at 72 hours after thrombin injection, correlating closely with the increase in ICAM-1 expression except the changes at 24 hours. CONCLUSION: The increased expression of ICAM-1 after thrombin injection is correlated with the degree of the neutrophil infiltration in the brain tissue around the thrombin injection zone, indicating thrombin is important to produce secondary brain damage after cerebral hemorrhage.
Subject(s)
Cerebral Hemorrhage/metabolism , Intercellular Adhesion Molecule-1/metabolism , Neutrophil Infiltration , Thrombin/pharmacology , Animals , Cerebral Hemorrhage/pathology , Disease Models, Animal , Male , Neutrophil Infiltration/drug effects , Random Allocation , Rats , Rats, WistarABSTRACT
OBJECTIVE: To observe the changes of noradrenaline (NE) content dynamically in the homogenate of rat brain tissues during experimental intracerebral hemorrhage (ICH), so as to understand the role of NE in secondary brain injury. METHODS: Seventy Wistar rats were randomly assigned into sham operation group and ICH group, each group subdivided into different time phase points as pre-operation, 0.5, 6, 12, 24, 48 and 72 h post-operation groups (n=5). ICH model was established by injection of collagenase and heparin into rat caudate nucleus, and the changes of NE content in the peripheral tissues of the hematoma, hypothalamus and brainstem were observed respectively at following time points as before operation and 0.5, 6, 12, 48 and 72 h after the operation. NE was determined by high-performance liquid chromatography. RESULTS: NE activities in the peripheral tissues of the hematoma, hypothalamus and brainstem increased synchronously 0.5 h after operation, peaked at 24 h, and then began to decline at 48 h. At the same time, the neurobehavioral score varied synchronously together with NE. CONCLUSION: NE is involved in the pathogenesis of secondary damage of the brain during ICH.
ABSTRACT
BACKGROUND: Frequency of poststroke cognitive impairment is high in western countries, and the risk factors of poststroke cognitive impairment have not been fully understood yet. We sought to examine the frequency and risk factors of cognitive impairment after ischemic stroke in a large stroke cohort of China. METHODS: A total of 434 consecutive patients with ischemic stroke were enrolled. The cognitive status before and 3 months after stroke was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly and the Mini-Mental State Examination, respectively. Poststroke cognitive impairment was defined as cognitive impairment with concomitant stroke, stroke-related cognitive impairment was defined as cognitive impairment developing after index stroke, and cognitive impairment after first-ever stroke was defined as cognitive impairment developing after first-ever stroke. Logistic regression analysis was used to find the risk factors of cognitive impairment after stroke. RESULTS: (1) Frequency of poststroke cognitive impairment was 37.1%, that of stroke-related cognitive impairment was 32.2%, and that of cognitive impairment after first-ever stroke was 29.6%. (2) The patients with cognitive impairment more often had older age, low educational level, atrial fibrillation, prior stroke, everyday drinking, left carotid territory infarction, multiple lesions, embolism, and dysphasia. (3) The factors associated with poststroke cognitive impairment in logistic regression analysis were age (OR 1.215, 95% CI 1.163-1.268), low educational level (OR 2.023, 95% CI 1.171-3.494), prior stroke (OR 5.130, 95% CI 2.875-9.157), everyday drinking (OR 2.013, 95% CI 1.123-3.607), dysphasia (OR 3.994, 95% CI 1.749-9.120), and left carotid territory infarction (OR 2.685, 95% CI 1.595-4.521). CONCLUSIONS: Cognitive impairment is common 3 months after ischemic stroke in Chinese people. Risk factors for poststroke cognitive impairment include age, low educational level, everyday drinking, prior stroke, dysphasia, and left carotid territory infarction.
Subject(s)
Brain Ischemia/complications , Brain Ischemia/epidemiology , Cognition Disorders/epidemiology , Cognition Disorders/etiology , Stroke/complications , Stroke/epidemiology , Aged , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/epidemiology , China/epidemiology , Cohort Studies , Female , Humans , Logistic Models , Male , Neuropsychological Tests , Risk Factors , Urban PopulationABSTRACT
OBJECTIVE: We studied a large hospitalized cohort of patients aged 55 years and over with acute ischemic stroke to identify the frequency and predictors of poststroke dementia. METHODS: A total of 434 consecutive patients with ischemic stroke were enrolled in this study. During admission, the demographic data, vascular risk factors, stroke features, and neurological status information were collected. All subjects were examined by a battery of neuropsychological tests during admission and 3 months after stroke. Logistic regression analysis was used to find the predictors of poststroke dementia. RESULTS: (1) The frequency of poststroke dementia was 27.2%, that of stroke-related dementia was 21.6%, and that of dementia after first-ever stroke was 22.7% 3 months after stroke. (2) Univariate analysis indicated that older age, low educational level (Subject(s)
Brain Ischemia/epidemiology
, Dementia, Vascular/epidemiology
, Stroke/epidemiology
, Aged
, Aged, 80 and over
, Brain Ischemia/complications
, Brain Ischemia/pathology
, Chi-Square Distribution
, China/epidemiology
, Cohort Studies
, Confidence Intervals
, Dementia, Vascular/etiology
, Dementia, Vascular/pathology
, Female
, Follow-Up Studies
, Humans
, Logistic Models
, Male
, Middle Aged
, Odds Ratio
, Predictive Value of Tests
, Socioeconomic Factors
, Stroke/complications
, Stroke/pathology
ABSTRACT
OBJECTIVE: To evaluate the significance of changes of neuropeptide Y (NPY) activity in plasma and brain tissue during experimental intracerebral hemorrhage (ICH). METHODS: Seventy Wistar rats were randomly divided into two groups: control group and ICH group with each group subdivided into preoperation, 0.5 hours, 6 hours, 12 hours,24 hours, 48 hours and 72 hours postoperation subgroups, respectively (n=5). The ICH was established by infusing collagenase and heparin into rat caudate. The changes of NPY in plasma and perihemotoma at preoperation, 0.5 hours, 6 hours, 12 hours, 24 hours, 48 hours and 72 hours after operation were observed, respectively. NPY was determined by radio-immunoassay. The morphologic change of brain was detected. RESULTS: NPY activity in plasma and perihematoma increased synchronously after cerebral hemorrhage, and peaked at 24 hours, then began to reduce in 48 hours, it was still higher than those of preoperation at 72 hours after hemorrhage (P<0.05 or P<0.01). The correspondent pathological changes were observed in brain tissue under light microscope and electron microscope. CONCLUSION: NPY might be involved in the pathogenesis of cerebral hemorrhage.
Subject(s)
Cerebral Hemorrhage/pathology , Neuropeptide Y/analysis , Animals , Brain/metabolism , Brain/pathology , Brain/ultrastructure , Brain Chemistry , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/metabolism , Female , Immunohistochemistry , Male , Microscopy, Electron , Neuropeptide Y/blood , Random Allocation , Rats , Rats, WistarABSTRACT
OBJECTIVE: To investigate the features of glutamate activity in the limbic system and the effects of glutamate on the activation of the hypothalamus-pituitary-adrenal (HPA) axis throughout both acute cerebral ischemia and reperfusion. METHODS: The changes in glutamate content in the nervous cell gap, in corticotrophin releasing hormone (CHR) mRNA expression level in brain tissue, and in adrenocorticotropic hormone in blood plasma at different time-points after middle cerebral artery occlusion (MCAO) in rats were determined respectively with high-performance liquid chomatography (HPLC) and in situ hybridization. RESULTS: Glutamate content in the hippocampus and the hypothalamus increased rapidly at ischemia 15 minutes, and reached peak value (the averages were 21.05 mg/g +/- 2.88 mg/g and 14.20 mg/g +/- 2.58 mg/g, respectively) at 1 hour after middle cerebral artery occlusion. During recirculation, it returned rapidly to the baseline level. At 24 hours after reperfusion, it went up once more, and remained at a relative high level until 48 hours after reperfusion, and then declined gradually. CRH mRNA expression levels in the temporal cortex, hippocampus and hypothalamus were enhanced markedly at 1 hour ischemia and were maintained until 96 hours after reperfusion. At the same time, adrenocorticotropic hormone level in plasma was relatively increased. In the peak stage of reperfusion injury, there was a significantly positive correlation (n = 15, r = 0.566, P < 0.05) of the glutamate contents in the hypothalamus with the number of cells positive for CRH mRNA expression level in the hypothalamus. CONCLUSION: It is probable that the CRH system in the central nervous system is mainly distributed in the limbic system, and glutamate might be one of the trigger factors to induce excessive stress response in the HPA axis.
Subject(s)
Glutamic Acid/analysis , Hypothalamo-Hypophyseal System/chemistry , Infarction, Middle Cerebral Artery/physiopathology , Limbic System/chemistry , Pituitary-Adrenal System/chemistry , Animals , Infarction, Middle Cerebral Artery/metabolism , Male , Rats , Rats, Wistar , Reperfusion Injury/metabolism , Reperfusion Injury/physiopathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the features of glutamate activity in the limbic system and the effects of glutamate on the activation of the hypothalamus-pituitary-adrenal (HPA) axis throughout both acute cerebral ischemia and reperfusion.</p><p><b>METHODS</b>The changes in glutamate content in the nervous cell gap, in corticotrophin releasing hormone (CHR) mRNA expression level in brain tissue, and in adrenocorticotropic hormone in blood plasma at different time-points after middle cerebral artery occlusion (MCAO) in rats were determined respectively with high-performance liquid chomatography (HPLC) and in situ hybridization.</p><p><b>RESULTS</b>Glutamate content in the hippocampus and the hypothalamus increased rapidly at ischemia 15 minutes, and reached peak value (the averages were 21.05 mg/g +/- 2.88 mg/g and 14.20 mg/g +/- 2.58 mg/g, respectively) at 1 hour after middle cerebral artery occlusion. During recirculation, it returned rapidly to the baseline level. At 24 hours after reperfusion, it went up once more, and remained at a relative high level until 48 hours after reperfusion, and then declined gradually. CRH mRNA expression levels in the temporal cortex, hippocampus and hypothalamus were enhanced markedly at 1 hour ischemia and were maintained until 96 hours after reperfusion. At the same time, adrenocorticotropic hormone level in plasma was relatively increased. In the peak stage of reperfusion injury, there was a significantly positive correlation (n = 15, r = 0.566, P < 0.05) of the glutamate contents in the hypothalamus with the number of cells positive for CRH mRNA expression level in the hypothalamus.</p><p><b>CONCLUSION</b>It is probable that the CRH system in the central nervous system is mainly distributed in the limbic system, and glutamate might be one of the trigger factors to induce excessive stress response in the HPA axis.</p>