To introduce the application of generalized multifactor dimensionality reduction (GMDR) method for detecting interactions, especially gene-gene interactions for quantitative traits. Principles, basic steps as well as features of GMDR were discussed, illustrated with a practical research case. As an interaction analysis method, GMDR was model-free, available for studies on different outcome variables including continuous ones, and permitted adjustment for covariates to improve prediction accuracy. Evidences of its capacity had been supposed by research on different diseases, e.g. nicotine dependence. GMDR method was applicable to different types of samples and outcome variables, which was superior to other statistical approaches for continuous variables in some aspects.

OBJECTIVE To determine the functional role of hydrogen sulfide (H2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca2 +/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) using wild type and CSE knockout mouse models. METHODS Continuous subcutaneous injection isoprenaline (7.5 mg·kg-1·d-1), once a day for 4 weeks to induce heart failure in Male C57BL/6 (6-8 weeks old) mice and CSE-/- mice. 150 μmol·L-1 H2O2 was used to induce oxidative stress in H9c2 cells. Echocardiograph was used to detect cardiac parameters. H&E stain and Masson stain was to observation histopathological changes. Western blot was used to detect protein expression and activity. The siRNA was used to silence protein expression. HPLC was used to detect H2S level. Biotin assay was used to detect the level of S- sulfhydration protein. RESULTS Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H2S levels, attenuated the development of heart failure in animals, reduced lipid peroxidation, and preserved mitochondrial function. The inhibition CaMKⅡ phosphorylation by SPRC and NaHS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds. Interestingly, CaMKⅡ activity was found to be elevated in CSE-/- mice as compared to wild type animals and the phosphorylation status of CaMKⅡ appeared to relate to the severity of heart failure. Importantly, in wild type mice SPRC was found to promote S-sulfhydration of CaMKII leading to reduced activity of this protein however, in CSE-/- mice S-sulfhydration was abolished following SPRC treatment. CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKⅡ is presented. SPRC mediated S-sulfhydration of CaMKII was found to inhibit CaMKⅡ activity and to preserve cardiovascular homeostasis.

OBJECTIVE To determine the functional role of hydrogen sulfide (H2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca2 +/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) using wild type and CSE knockout mouse models. METHODS Continuous subcutaneous injection isoprenaline (7.5 mg·kg-1 per day), once a day for 4 weeks to induce heart failure in male C57BL/6 (6-8 weeks old) mice and CSE-/- mice. 150 μmol·L-1 H2O2 was used to induce oxidative stress in H9c2 cells. Echocardiograph was used to detect cardiac parameters. H&E stain and Masson stain was to observation histopathological changes. Western blot was used to detect protein expression and activity. The siRNA was used to silence protein expression. HPLC was used to detect H2S level. Biotin assay was used to detect the level of S-sulfhydration protein. RESULTS Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H2S levels, attenuated the development of heart failure in animals, reduced lipid peroxidation, and preserved mitochondrial function. The inhibition CaMKⅡ phosphorylation by SPRC and NaHS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds. Interestingly, CaMKⅡ activity was found to be elevated in CSE-/- mice as compared to wild type animals and the phosphorylation status of CaMK Ⅱ appeared to relate to the severity of heart failure. Importantly, in wild type mice SPRC was found to promote S-sulfhydration of CaMKⅡ leading to reduced activity of this protein however, in CSE-/- mice S-sulfhydration was abolished following SPRC treatment. CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKⅡ is presented. SPRC mediated S-sulfhydration of CaMKⅡ was found to inhibit CaMKⅡ activity and to preserve cardiovascular homeostasis.

OBJECTIVETo estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology.

METHODSCadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary beta2-microgloburin (B2M), N-acetyl-13-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD.

RESULTSThe cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG; and ALB) and exposure biomarker (UCd). BEL value was 5 microg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 microg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected.

CONCLUSIONBMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

Acetylglucosaminidase ; urine ; Albuminuria ; urine ; Biomarkers ; urine ; Cadmium ; toxicity ; urine ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Occupational Exposure ; Spectrophotometry, Atomic ; beta 2-Microglobulin ; urine

OBJECTIVEBased on two sets of data from occupational epidemiology, Benchmark dose (BMD) was applied to estimate biological exposure limit (BEL).

METHODSCadmium exposed workers were selected from a cadmium smelting and a zinc products factory and control group was selected from doctors or nurses and staff from shops living in the same area; Urinary cadmium (UCd) was used as exposure biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB) were as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD.

RESULTSCalculated abnormal prevalence was based on the upper limit of 95% of effect biomarkers in control group; There are significant dose response relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g creatinine for UNAG as effect biomarker; BEL can be estimated by using the method of BMD; the more sensitive biomarker would used, the more occupational people would protected.

CONCLUSIONThe application of BMD in estimating biological exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to be used to estimate BEL for cadmium exposure.

Acetylglucosaminidase ; urine ; Albuminuria ; urine ; Biomarkers ; urine ; Cadmium ; adverse effects ; urine ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Occupational Exposure ; Reference Values ; beta 2-Microglobulin ; urine

Objective To compare the ability and influence factors of three platelet function tests:light transmission aggregometry (LTA),thrombelastograph (TEG) and VerifyNow.Methods A total of 174 patients underwent percutaneous coronary intervention (PCI) and platelet function test were enrolled.Platelet function were tested by LTA,TEG and VerifyNow.Results Patients were found to be high platelet reactivity (HPR) by LTA (56.64％,64 cases/113 cases),TEG(60.38％,32 cases/52 cases),VerifyNow (17.24％,15 cases /87 cases).There were no significant differences observed between TEG and LTA (P ＞0.05).VerifyNow identified lower HPR proportion compared with TEG and LTA (all P ＜ 0.001).Conclusion Compared with LTA and TEG,VerifyNow identified lower HPR proportion and may overestimate the effectiveness of clopidogrel.We will follow the patients to study the predictive capability of three tests.

Objective To assess the characteristics of executive dysfunction in patients with hepatolenticular degeneration (HLD) through neuropsychological tests and explore its mechanism. Methods One hundred and two patients with HLD were chosen and divided into CT/MRI positive (n=70) and CT/MRI negative (n=32) groups in accordance with cerebral imaging and the other 30 healthy subjects were selected as normal control group. These three groups were recorded the results of such imaging data as Raven's standard progressive matrices (R'SPM) test, Stroop color-word test (CWT), trail making test (TMT). Results Imaging data indicated a statistical change of frontal-striatal loops in patients with HLD. Significant differences of the total scores, perception discrimination, serial relationship and abstract reasoning of R'SPM test were showed in the three groups and the word interference time of CWT, B items time-consuming and interference effects of TMT in these groups were statistically different (P<0.05). Conclusion Executive dysfunction appears commonly in patients with HLD. The CT/MRI positive group showed a more serious degree and area of the damage as compared to that in the CT/MRI negative group. Damages of frontal-striatal loops may be one of the important mechanisms of executive dysfunction in patients with HLD.

OBJECTIVE: To develop a self-administered risk questionnaire for common nutrition-related diseases in middle school students. METHODS: Two phases were conducted to develop the questionnaire: scale development and validation. Phase 1 included 7 steps: (1) determining the objective, theoretical framework, principles and format for indicator generation; (2) setting up the preliminary indicator pool; (3) selecting indicators and forming pilot questionnaire through focus groups; (4) testing the pilot questionnaire; (5) further correcting the questionnaire using expert consultation; (6) choosing indicators again using good-poor analysis; and (7) shaping the final questionnaire. Phase 2 consisted of: (1) using the Pearson correlation coefficient to assess test-retest reliability; (2) using the Cronbach's alpha coefficient to assess the internal consistency reliability; (3) using the feedback from field investigation to assess face validity; and (4) using explanatory factor analysis to assess construct validity. Students from 96 classes were selected at random in Hunan Province as the field test samples using stratified sampling and cluster sampling. And the students from 4 out of the 96 classes were chosen again to serve as the test-retest samples. We used Epidata 3.0 to build the database and SPSS 11.0 to analyze the data. RESULTS: A brief self-administered risk questionnaire for common nutrition-related diseases in middle school students with 12 items being formed after Phase 1. Good-poor analysis showed results from t tests for each item were statistically significant (P<0.05). The Pearson correlation coefficient was 0.76 (P<0.05) and the Cronbach's alpha coefficient was 0.56. The questionnaire was accepted by the students participating in the field test. Four common factors were extracted using explanatory factor analysis, accounting for 50.18% of the total variation. CONCLUSION The brief self-administered risk questionnaire for common nutrition-related diseases in middle school students is reliable and valid.
Adolescent ; Adult ; Child ; China ; epidemiology ; Female ; Humans ; Male ; Malnutrition ; epidemiology ; Nutrition Surveys ; Obesity ; epidemiology ; Risk Assessment ; Self Administration ; methods ; Students ; Surveys and Questionnaires

BACKGROUNDNeuroimaging studies have found that functional changes exist in patients with Parkinson's disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.

METHODSSeventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.

RESULTSCompared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).

CONCLUSIONSThe baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease's progression in patients with PD.

Adult ; Aged ; Brain ; pathology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Parkinson Disease ; diagnosis

OBJECTIVETo investigate the effects and the related mechanisms of the components of Dang-Gui-Bu-Xue decoction (DGBXD) on improving blood deficiency.

METHODThe effects of promoting hematopoietic function were observed with the blood difficient model mice, by giving components of DGBXD. RBC, WBC, reticulocytes and bone marrow nucleated cells (BMNC) were determined. The components of DGBXD on proliferation of BMNC and on clony forming unit (CFU) were also determined.

RESULTThe components of DGBXD remarkably increased the quantity of RBC, WBC, and BMNC. Some of the components promoted the proliferation of BMNC and increased the quantity of CFU-Mix. Among them, polysaccharide of angelica was most potent.

CONCLUSIONThe studies show that the extracts and some components of DGBXD can promote the hemopoietic function system of the model mice, and they exert the effects in a comprehensive way.

Angelica sinensis ; chemistry ; Animals ; Astragalus membranaceus ; chemistry ; Blood Cell Count ; Bone Marrow Cells ; drug effects ; Colony-Forming Units Assay ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hematopoietic Stem Cells ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Phytotherapy ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology