Prognostic Value for the Risk Stratification of Circulating Monocyte Subsets Combining Left Ventricular Ejection Fraction in Patients With Acute ST-segment Elevation Myocardial Infarction / 中国循环杂志

Objective:To explore the prognostic value for circulating monocyte subsets combining left ventricular ejection fraction (LVEF) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:STEMI patients admitted within 24 h of onset received PCI in Pingjin hospital heart center were enrolled.Flow cytometry (FCM) was used to examine 3 subsets of monocyte in peripheral blood as classical CD14++CD16-monocyte,intermediate CD14++CD16+ monocyte and non-classical CD14+CD16++ monocyte.The patients were followedup in 3 years for major adverse cardiac events (MACE) occurrence.The relationship between monocyte subsets,LVEF and MACE occurrence was studied by COX model analysis and MACE prediction model was established by ROC combining multivariate Logistic regression analysis.Results:There were 50/221 patients suffered from MACE during 3-year follow-up period.Compared with Non-MACE patients,MACE patients had the elder age (63.82±11.88) years vs (58.84±11.40) years,P=0.009;more diabetes mellitus (28.0％ vs 18.7％),P＜0.001;higher blood levels of LDL-C (2.77 mmol/L) vs (2.41 mmol/L),P=0.003 and CD14++CD16+ monocyte (47.17 cells/μl) vs (21.47 cells/μl),P＜0.001;lower LVEF (52％ vs 46％),P＜0.001.Multivariate Cox analysis indicated that CD14++CD16+ (HR=2.211,95％ CI 1.211-3.635,P=0.016) and LVEF (HR=2.014,95％ CI 1.038-2.933,P=0.022) were the independent risk factors for MACE occurrence in STEMI patients.ROC combining multivariate Logistic regression analysis presented that MACE predictive value of CD14++CD16+ monocyte combining LVEF (AUC=0.744,95％ CI 0.664-0.823,P＜0.001) was higher than the single value of CD14++CD16+ monocyte (AUC=0.683,95％ CI 0.598-0.768,P＜0.001) and LVEF(AUC=0.640,95％ CI 0.552-0.7291,P=0.003) respectively.Conclusion:Circulating level of CD14++CD16+ monocyte combining LVEF may predict MACE occurrence within 3 years in STEMI patients;it had potential value in clinical practice.

Prognostic Value for the Risk Stratification of Circulating Monocyte Subsets Combining Left Ventricular Ejection Fraction in Patients With Acute ST-segment Elevation Myocardial Infarction / 中国循环杂志

Objective:To explore the prognostic value for circulating monocyte subsets combining left ventricular ejection fraction (LVEF) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:STEMI patients admitted within 24 h of onset received PCI in Pingjin hospital heart center were enrolled.Flow cytometry (FCM) was used to examine 3 subsets of monocyte in peripheral blood as classical CD14++CD16-monocyte,intermediate CD14++CD16+ monocyte and non-classical CD14+CD16++ monocyte.The patients were followedup in 3 years for major adverse cardiac events (MACE) occurrence.The relationship between monocyte subsets,LVEF and MACE occurrence was studied by COX model analysis and MACE prediction model was established by ROC combining multivariate Logistic regression analysis.Results:There were 50/221 patients suffered from MACE during 3-year follow-up period.Compared with Non-MACE patients,MACE patients had the elder age (63.82±11.88) years vs (58.84±11.40) years,P=0.009;more diabetes mellitus (28.0％ vs 18.7％),P＜0.001;higher blood levels of LDL-C (2.77 mmol/L) vs (2.41 mmol/L),P=0.003 and CD14++CD16+ monocyte (47.17 cells/μl) vs (21.47 cells/μl),P＜0.001;lower LVEF (52％ vs 46％),P＜0.001.Multivariate Cox analysis indicated that CD14++CD16+ (HR=2.211,95％ CI 1.211-3.635,P=0.016) and LVEF (HR=2.014,95％ CI 1.038-2.933,P=0.022) were the independent risk factors for MACE occurrence in STEMI patients.ROC combining multivariate Logistic regression analysis presented that MACE predictive value of CD14++CD16+ monocyte combining LVEF (AUC=0.744,95％ CI 0.664-0.823,P＜0.001) was higher than the single value of CD14++CD16+ monocyte (AUC=0.683,95％ CI 0.598-0.768,P＜0.001) and LVEF(AUC=0.640,95％ CI 0.552-0.7291,P=0.003) respectively.Conclusion:Circulating level of CD14++CD16+ monocyte combining LVEF may predict MACE occurrence within 3 years in STEMI patients;it had potential value in clinical practice.

Correlation between cognitive functions and syndromes of traditional Chinese medicine in amnestic mild cognitive impairment.

OBJECTIVE: To explore the correlation between the cognitive functions and syndromes of traditional Chinese medicine (TCM) in amnestic mild cognitive impairment (aMCI), and to provide evidence for clinical syndrome differentiation treatment. METHODS: Six hundred subjects from Dongzhimen Hospital and seven communities in Beijing, aged between 40 and 85 years, accepted neuropsychological assessments, imaging and biochemical examinations, and syndrome differentiation, from whom 159 aMCI patients, 213 normal control (NC) subjects and 171 Alzheimer's dementia (AD) patients were screened out. Correlation between the cognitive functions and TCM syndromes in aMCI patients was analyzed. RESULTS: Mini-Mental State Examination (MMSE) score in aMCI patients was closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.11; P = 0.003, P = 0.015). Delayed Word Recall (DWR) score was correlated with kidney essence vacuity (r = -0.20, P = 0.020). Instant Story Recall (ISR) and Delayed Story Recall (DSR) scores were respectively correlated with turbid phlegm blocking upper orifices (r = -0.11, r = -0.27; P = 0.021, P = 0.000). Language function was correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.13; P = 0.042, P = 0.007). Attention/calculation was also closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.10, r = -0.21; P = 0.039, P = 0.010). Attention score of aMCI patients was correlated with excess of heat toxin syndrome (r = -0.29, P = 0.026). CONCLUSION: The memory decline of aMCI is correlated with kidney essence vacuity and turbid phlegm blocking upper orifices. Furthermore, turbid phlegm blocking upper orifices is correlated with episodic memory decline, which is closely related to AD. The aMCI patients with phlegm have the risk to progress into AD. Although other cognitive functions of aMCI remain relatively intact, the patients' language function, attention/calculation and the whole cognitive function may be worsen as the aggravation of kidney essence vacuity, deficiency of blood and qi, phlegm and heat toxin, and may eventually lead to multiple cognitive domains impairment, even dementia.

Development of a universal high-throughput calcium assay for G-protein- coupled receptors with promiscuous G-protein Galpha15/16.

AIM: To develop a universal high-throughput screening assay based on Galpha15/16- mediated calcium mobilization for the identification of novel modulators of Gprotein- coupled receptors (GPCR). METHODS: In the present study, CHO-K1 or HEK293 cells were co-transfected with plasmids encoding promiscuous G-protein Galpha15/16 and various receptors originally coupled to Galphas, Galphai, or Galphaq pathways. Intracellular calcium change was monitored with fluorescent dye Fluo-4. RESULTS: We found out for all the receptors tested, Galpha15/16 could shift the receptorso coupling to the calcium mobilization pathway, and the EC50 values of the ligands generated with this method were comparable with reported values that were obtained using traditional methods. This assay was validated and optimized with the zeta-opioid receptor, which originally coupled to Galphai and was recently found to play important roles in neurodegenerative and autoimmune diseases. A largescale screening of 48 000 compounds was performed based on this system. Several new modulators were identified and confirmed with the traditional GTPgammaS binding assay. CONCLUSION: This cell-based calcium assay was proved to be robust and easy to automate, and could be used as a universal method in searching for GPCR modulators.

[Guiding principles of clinical research on mild cognitive impairment (protocol)].

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.

[An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)"].

In order to provide the "guiding principles of clinical research on mild cognitive impairment (MCI) (protocol)" edited by Beijing United Study Group on MCI of the Capital Foundation of Medical Developments (CFMD) with evidence support, clinical criteria, subtypes, inclusion and exclusion of MCI, and use of rating scales were reviewed. The authors suggested that MCI clinical criteria and new diagnosis procedure from the MCI Working Group of the European Alzheimer's disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Diagnostic rating scales including Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Instrumental Activities of Daily Living (IADL) are very useful in definition of MCI but can not replace its clinical criteria. Absence of major repercussions on daily life in patients with MCI was emphasized, but the patients may have minimal impairment in complex IADL. According to their previous research, the authors concluded that highly recommendable neuropsychological scales with cut-off scores in the screening of MCI cases should include Mini-Mental State Examination (MMSE), logistic memory test such as Delayed Story Recall (DSR), executive function test such as Clock Draw Test (CDT), language test such as Verbal Category Fluency Test (VCFT), etc. And finally, the detection of biological and neuroimaging changes, including atrophy in hippocampus or medial temporal lobe in patients with MCI, was introduced.