GLP-1 plays a protective role in hippocampal neuronal cells by activating cAMP-CREB-BDNF signaling pathway against CORT+HG-induced toxicity.

Major depressive disorder (MDD) with diabetes mellitus (DM) significantly reduces the quality of the patient's life, and currently, there is no effective treatment. This study explored the feasibility of Glucagon-like peptide-1 (GLP-1) in treating MDD combined with DM. The protective effects of GLP-1 on mouse hippocampal neuronal cell line HT22 cultured with corticosterone (CORT) and high glucose (HG) were assessed. HT22 cells were cultured with CORT + HG to construct a cell model of MDD combined with DM. Cell viability and cell apoptosis/necrocytosis were detected by CCK-8 assay and flow cytometry/confocal laser scanning microscopy, respectively, after treatment with GLP-1. In addition, BDNF and neurotransmitter levels, lactic dehydrogenase (LDH) and glucose levels, and proteins of cAMP-CREB-BDNF signal pathway in the culture supernatants were measured through an enzyme-linked immunosorbent assay and colorimetric assays and Western blot, respectively. The ideal intervention combination to construct a cell model of MDD combined with DM was CORT 200 µM and HG 50 mM for 48 h. After treatment of 50 nM GLP-1 for 48 h, the model+50 nM GLP-1 group's apoptosis and necrocytosis rates and LDH and glucose concentrations in the culture supernatants decreased significantly compared with the model group. However, the BDNF, 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), PKA, p-CREB, and p-Trkb concentrations in the culture supernatants increased significantly. GLP-1 functioned against CORT + HG-induced toxicity by activating the cAMP-CREB-BDNF signaling pathway in hippocampal neuronal cells.

Neuroticism and Fatigue 3 Months After Ischemic Stroke: A Cross-Sectional Study.

OBJECTIVE: To examine the relation between neuroticism and fatigue in Chinese patients with stroke. DESIGN: Cross-sectional study. SETTING: Acute stroke unit. PARTICIPANTS: Survivors of ischemic stroke (N=191) recruited from the acute stroke unit between May 1, 2010, and September 1, 2011. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The personality trait of neuroticism was measured with the neuroticism subscale of the Chinese version of the NEO Five-Factor Inventory. The level of fatigue was measured with the Fatigue Assessment Scale. The National Institutes of Health Stroke Scale, Geriatric Depression Scale, Barthel Index, and Mini-Mental State Examination were administered to obtain demographic and clinical information. RESULTS: Fatigue severity 3 months after stroke positively correlated with Geriatric Depression Scale and NEO Five-Factor Inventory neuroticism scores and negatively correlated with the Barthel Index score. CONCLUSIONS: Neuroticism, independent of depressive symptoms, is a predictor of fatigue severity 3 months after stroke. Interventions such as psychological screening programs are warranted for early detection of patients at high risk of poststroke depression.

Poststroke agitation and aggression and social quality of life: a case control study.

BACKGROUND AND OBJECTIVE: Aggression and agitation are common after a stroke. The association between agitation/aggression following stroke and Health-Related Quality of Life (HRQoL) in stroke survivors is unknown. This study aimed to examine the association between agitation/aggression and HRQoL in Chinese stroke survivors. METHODS: Three hundred and twenty-four stroke patients entered this cross-sectional study. Agitation/aggression was assessed using the Chinese version of Neuropsychiatric Inventory (CNPI). HRQoL was measured with the Stroke Specific Quality of Life (SSQoL). RESULTS: Three months after the index stroke, agitation/aggression was found in 60 (18.5%) patients. In the agitation/aggression group, 44 patients (73.3%) showed passive agitation/aggression, whereas 16 (26.7%) displayed passive and active agitation/aggression. No patients showed only active agitation/aggression. Patients with agitation/aggression were more likely to have history of diabetes and greater severity of depression, as well as lower SSQoL total score and Personality Changes and Social Role scores. Controlling for diabetes and depression severity did not alter the above results. The Energy and Thinking scores of the SSQoL were significantly lower in the passive/active agitation/aggression group relative to the passive agitation/aggression group (adjusted for CNPI aggression/agitation score). CONCLUSION: In this study sample, agitation/aggression was preponderantly of the passive type and was associated with poorer HRQoL independently from depression or medical conditions. Patients with both passive and active agitation/aggression had lower Quality of Life (QoL) than patients with only passive agitation/aggression. The causality of the association between low QoL and agitation/aggression needs to be explored in future studies.

Location of Acute Infarcts and Agitation and Aggression in Stroke.

The role of the infarct location in the development of poststroke agitation (PSA) is largely unknown. This study examined the association between the locations of infarcts and PSA at 9 months following the index stroke in 213 patients with the Chinese version of the Neuropsychiatric Inventory. Compared with the non-PSA group, PSA patients had a higher number and volume of acute pontine infarcts. Ventral pontine and lateral cerebellar infarcts were independent predictors of PSA in the multivariate analysis.

Brainstem infarcts predict REM sleep behavior disorder in acute ischemic stroke.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disturbance in which patients enact their dreams while in REM sleep. The behavior is typically violent in association with violent dream content, so serious harm can be done to the patient or the bed partner. The prevalence of RBD is well-known in Parkinson's disease, Lewy body dementia, and multiple systems atrophy. However, its prevalence and causes in stroke remained unclear. The aim of this study was to determine factors influencing the appearance of RBD in a prospective cohort of patients with acute ischemic stroke. METHODS: A total of 2,024 patients with first-ever or recurrent acute ischemic stroke were admitted to the Acute Stroke Unit at the Prince of Wales Hospital between January 2010 and November 2011; 775 of them received an MRI scan. Within 2 days of admission, a research nurse collected demographic and clinical data and assessed the severity of each stroke using the National Institute of Health Stroke Scale (NIHSS). One hundred and nineteen of the 775 patients meeting study entry criteria formed the study sample. All eligible participants were invited to attend a research clinic 3 months after the onset of the index stroke. In the attendance, a research assistant administered the MMSE and the 13-item RBD questionnaire (RBDQ). RESULTS: Among 119 stroke patients, 10.9% were exhibited RBD, defined as an REM sleep behavior disorder questionnaire score of 19 or above. The proportion of patients with acute brainstem infarct was significantly higher in RBD patients than those without RBD. Compared with patients without RBD, RBD patients were more likely to have brainstem infarcts and had smaller infarct volumes. In a multivariate analysis, in which stroke location and infarct volume were inserted, brainstem infarcts were an independent predictor of RBD (odds ratio = 3.686; P = 0.032). CONCLUSIONS: The results support the notion of a predominant role of brainstem injury in the development of RBD and suggest that patients with brainstem infarcts RBD should be evaluated by a clinical neurologist.

Cerebral microbleeds and fatigue in stroke.

BACKGROUND AND PURPOSE: Poststroke fatigue (PSF) is a frequent and persistent problem in stroke survivors. The neuroanatomical model of PSF remains unclear. This study examined the association between PSF and cerebral microbleeds (CMBs). METHODS: The sample comprised 199 patients with acute ischemic stroke. A psychiatrist who was blind to the subjects' radiological data administered the Chinese version of the Fatigue Severity Scale. PSF was defined as a Fatigue Severity Scale score of 4.0 or more. The locations of CMBs were evaluated with magnetic resonance imaging within 7 days of admission. RESULTS: Of the 199 patients screened, 47 (23.6%) had PSF. The PSF group had a higher Geriatric Depression Scale score (p < 0.001) and a trend for a higher age (p = 0.074). The proportion of patients with deep CMBs was significantly higher in the PSF group (66.0 vs. 48.7%; p = 0.038). The presence of deep CMBs was a significant independent predictor of PSF with an odds ratio of 2.68 (p = 0.016). CONCLUSION: The results suggest that deep CMBs are associated with a higher risk of PSF. Further studies are needed to clarify whether CMBs affect the clinical presentation, treatment response and outcome of PSF.

[Relations between serum homocysteinemia and carotid artery plaques].

OBJECTIVE: To explore the relation between homocysteinemia (HCY) and carotid artery plaque. METHODS: Subjects were derived from a cohort of Kailuan study, which was a community-based and cross-sectional. From June 2010 to June 2011, a total of 5852 subjects were selected from 101 510 working or retired employees at the Tangshan Kailuan Company in 2006 - 2007. Data was extracted from the results of health examination on the employees. Selecting process was carried out by those staff working on the clinical trials on stroke and from the research center of Tiantan Hospital, Capital Medical University. Subjects who were beyond 40 years of age but without histories as previous stroke, transient ischemic attack (TIA) or myocardial infarction were included and identified, to take part in the study through stratified random sampling. Finally, 5440 eligible subjects were enrolled and data from 5377 subjects were analyzed. All the information was obtained through unified questionnaire, blood tests and carotid artery ultrasonography. Multivariate logistic regression was used to analyze the factors related to carotid artery plagues. RESULTS: (1) The baseline results showed that the average age of the subjects (n = 5377) was 55.18 ± 11.78 years old with 3215 as males. All the subjects were divided into three groups by tertiles of HCY, with 1771 subjects in the first quartile group (HCY < 11.00 µmol/L), 1814 in the second quartile group (11.00-16.98 µmol/L) and 1792 in the third quartile group (≥ 16.98 µmol/L). 2300 subjects were identified as having carotid artery plaques. (2) The prevalence rates of carotid artery plaques in the three groups were 29.9%, 43.3% and 55.0% respectively. (3) After multivariable adjustment, the third quartile HCY was still serving as a risk factor, affecting the formation of carotid artery plaques, with the OR values as 1.344 (95%CI: 1.134 - 1.594). CONCLUSION: High HCY was related to the increased prevalence of carotid artery plaque and thus served as a risk factor for carotid artery plaque.

[Study on the inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus].

OBJECTIVE: To discuss the inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus. METHODS: Used SDS-PAGE electrophoresis, spectrophotometry and semiautomatic biochemistry analysis to detect the accumulated concentration of norfloxacin, membranin electrophoretogram and the enzymatic activity in extracellular fluid before and after Coptis extract disposition. RESULTS: The accumulated concentration of medicine norfloxacin within the experiment strains which treated with Coptis extract was clear higher than that of the blank space (P < 0.01); some proteins which molecular weights were in 35 - 38 kDa rebound expressed after Coptis extract treated; The extracellular fluid enzymic activities of resistant Staphylococcus aureus had no significant difference (P > 0.05). CONCLUSION: The inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus is the results of the combined action of various chemical composition and multi-target interaction, and the exact molecular mechanism remains to be further researched.

Removal of antibiotic resistance of live vaccine strain Escherichia coli MM-3 and evaluation of the immunogenicity of the new strain.

MM-3 was a live vaccine strain candidate for protecting neonatal piglets from diarrhea. Designed in the 1980s, a high degree of protection from colibacillosis was afforded to piglets in a challenge study and field trials. However MM-3 had a drawback of carrying the antibiotic resistance gene (chloramphenicol acetyltransferase gene, cat). The introduction of a host-plasmid balanced lethal system into the vaccine was a good idea to solve the problem. The lambda-Red recombination system was adopted in this study to realize the replacement of cat by aspartate-semialdehyde dehydrogenase gene (asd) in the plasmid pMM085. The new plasmid named pMMASD was introduced into an Escherichia coli strain chi6097 and Salmonella typhimurium chi4072 where the asd gene had been knocked out in their chromosomes. Cultured in an Erlenmeyer flask, expression levels of two antigens K88ac fimbriae and heat-labile enterotoxin B subunit (LTB) in cell lysate were similar among MM-3, chi4072(pMMASD) and chi6097(pMMASD). However, chi4072(pMMASD) possessed the more effective secretion mechanism to transport LTB enterotoxin into culture liquid. The relatively higher stability of pMMASD in Salmonella typhimurium chi4072 than that of pMM085 in MM-3 was determined both in vitro in the absence of selective pressure, and in vivo following oral inoculation. Oral immunization of BALB/c mice with chi4072(pMMASD) or chi6097(pMMASD) was sufficient to elicit IgA responses in mucosal tissues as well as systemic IgG antibody responses to the K88 fimbriae, while MM-3 failed to elicit specific antibody responses to K88 fimbriae in mucosal tissues. Among three live strains, only chi4072(pMMASD) could develop strong humoral responses against LTB enterotoxin. The results suggest that chi4072(pMMASD) is expected to be a promising live vaccine strain.

Construction of a novel Shigella live-vector strain co-expressing CS3 and LTB/STm of enterotoxigenic E.coli.

AIM: To construct and evaluate a polyvalent recombinant vaccine strain Shigella flexneri 2a T32 against enterotoxigenic E.coli (ETEC). METHODS: By using a host-plasmid balanced lethal system based on asd gene, a polyvalent recombinant strain was constructed to highly express CS3 and regularly express fusion enterotoxin of LTB subunit and mutant ST (LTB/STm) in a vaccine strain Shigella flexneri 2a T32 with specific deletion of asd gene. Fimbria CS3 was observed by immunofluorescence and electron microscopy assay. The security of LTB/STm was examined by ileal loop assay and suckling mouse assay. To evaluate this new candidate vaccine, it was compared with a previous vaccine strain in plasmid and protein level, growth assay and immunogenicity in Balb/c mice. RESULTS: The newly constructed vaccine expressed CS3 and grew better than the previously constructed vaccine except for the lower expression of LTB/STm. Serum IgG and mucosal IgA against CS3, LTB, ST, and host lipopolysaccharide (LPS) were produced after immunization of Balb/c mice by oral route with the new strain. The titers were not significantly different from the Balb/c mice with the previous strain. CONCLUSION: This novel candidate diarrheal vaccine can effectively induce serum and mucosal antibody responses against ETEC and Shigella.

[Effects of intermittent normobaric hypoxia training on heart rate variability].

OBJECTIVE: To observe the influences of intermittent normobaric hypoxia (INH) training on heart rate variability (HRV) under hypoxia. METHOD: Eight subjects were trained with INH for 4 weeks (24 d), subjects' HRV level, recorded during exposure to hypoxia (10% O2) before and after the training, were compared and analyzed. RESULT: After the INH training, average of normal to normal Intervals (R-R), standard deviation of normal to normal Intervals (SDNN), total power (TP), high frequency (HF) and low frequency (LF) increased significantly during hypoxia (P<0.05 - P<0.001); normalized low frequency (LFn), normalized high frequency (HFn) and LF/HF showed no significant change. CONCLUSION: 1) INH training can increase subjects' HRV under hypoxia; 2) INH training can not only be used to increase the tolerance of hypoxia, but it is also good for increasing astronaut's flying tolerance under special environment.