Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma.

BACKGROUND: Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from Curcuma species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma. METHODS: BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed. RESULTS: THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A). CONCLUSIONS: Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs.

Clinical nutrition knowledge, attitude and practice of medical interns in Shanghai: Contributory factors.

BACKGROUND AND OBJECTIVES: To provide a questionnaire, with Shanghai medical interns as respondents, analyzing knowledge (K), attitude (A), and practice (P) in relation to clinical nutrition, and to explore factors that could affect KAP scores. METHODS AND STUDY DESIGN: The cross- sectional study used 330 interns from Shanghai medical universities responding to general material data questionnaires and KAP questionnaires on clinical nutrition. RESULTS: The mean KAP score was 210.26±25.9 (X±SD), and the score for each part of the KAP questionnaire was just within the threshold for qualified. Multivariate analysis showed that the factors influencing the proportion of excellent scores for K were preventive medicine major (OR=3.45, p<0.001), senior intern (OR=2.52, p=0.002), and tertiary intern hospital (OR=2.31, p=0.006). The only factor influencing the proportion of excellent scores for P was accessing nutritional information one to three times per week (OR=3.95, p=0.011). Nutrition course had no relation to any scores of K, A, P. CONCLUSIONS: The mean scores of overall KAP and the individual K, A, P were all categorized as qualified. The P score was the lowest and only influenced by how frequently information was accessed. In summary, nutrition knowledge and regular practical training gained from intern hospital could be a better way to enable senior interns to quickly and competently address patient nutrition problems at the commencement of their careers.

Long intergenic noncoding RNA p21 suppresses the apoptosis of hippocampus neurons in streptozotocin-diabetic mice by sponging microRNA-221 through upregulation of FOS.

Diabetes is associated with neurological complications, and accumulated evidence shows that biological pathways in diabetes are targeted by noncoding RNA transcripts. In this study, the role of long intergenic noncoding RNA (lincRNA) p21/microRNA-221 (miR-221)/fructooligosaccharide (FOS) axis was investigated in the mice with diabetes treatment. The streptozotocin-induced diabetic mouse model was established. The learning ability and the pathological changes in mice were analyzed. After that, the interaction among miR-221, lincRNA p21, and FOS was explored and verified. The subcellular location of lincRNA p21 was identified. Finally, the cell cycle and apoptosis of the hippocampus neurons were measured. In the diabetic mice, the levels of blood glucose were higher and the leaning abilities were inhibited. miR-221 was highly expressed in the diabetic mice whereas lincRNA p21 and FOS were poorly expressed. miR-221 could bind with both lincRNA p21 and FOS. miR-221 silencing or lincRNA p21 overexpression in the diabetes mice reduced the cell apoptosis rate, and the expression of Bax and cleaved Caspase-3, whereas increase the Bcl-2 expression. Overexpression of lincRNA p21 promotes FOS expression by binding to miR-221, thereby, inhibiting hippocampal neuron apoptosis in diabetic mice. This may offer potential targets for diabetes.

Effect of micronutrient pack on micronutrient status and antioxidant capacities among institutional older adults in Shanghai, China.

BACKGROUND AND OBJECTIVES: Older adults are at increased risk of micronutrient deficiency, disrupting the balance of oxidation/antioxidation system and leading to serious health burdens. This study aimed to investigate the effect of micronutrient pack on micronutrient status and oxidative/antioxidative biomarkers in institutional older adults. METHODS AND STUDY DESIGN: Subjects aged 65-100 years were randomly assigned to either intervention group or control group (n=49 each), providing a package of micronutrient pack or placebo daily for three months. The concentrations of micronutrients, malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected both at baseline and at the end of the study. RESULTS: The changes in concentrations of serum folate (21.1±1.6 vs 0.6±0.5 nmol/L), vitamin B-1 (3.4±0.4 vs -0.2±0.3 nmol/L), vitamin B-2 (11.5±3.3 vs 2.3±1.4 nmol/L), vitamin B-12 (128.8±34.8 vs 13.3±16.0 pmol/L), 25-hydroxyvitamin D (17.8±1.3 vs -0.8±0.5 ng/mL) and plasma zinc (0.6±1.8 vs -9.6±1.9 µmol/L) over 3-months were significantly increased in the intervention group compared with the control group (all p<0.05). While the prevalence of folate, vitamin B-12 and vitamin D deficiencies were significantly decreased after 3-months intervention (all p<0.05). Moreover, changes in serum MDA level (-1.5±0.2 vs 0.2±0.3 nmol/mL) were remarkably reduced, and the activities of serum GSH-Px (1.3±0.3 vs 0.3±0.2 ng/mL) and plasma SOD (14.3±2.4 vs -2.1±2.4 U/mL) were increased in the intervention group than those of in the control group (all p<0.01). CONCLUSIONS: The micronutrient pack among institutional older adults was well-accepted with good compliance and tolerance. The 3-month intervention may improve micronutrient status and enhance antioxidative capacities.

Tetrahydrocurcumin, a major metabolite of curcumin, ameliorates allergic airway inflammation by attenuating Th2 response and suppressing the IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2 -Notch1/Notch2 pathways in asthmatic mice.

BACKGROUND: Curcumin (Cur), derived from Curcuma species, exhibits anti-inflammatory, antioxidant, and anticancer effects. Although Cur has some beneficial effects on asthma, its clinical application is limited by its low bioavailability. Tetrahydrocurcumin (THC), the major active metabolite of Cur, has multiple biological functions, similarly to Cur, and importantly, it showed enhanced bioavailability in tissues and plasma. However, the effect of THC on asthma has not been reported. OBJECTIVE: The current study sought to investigate the efficacy of dietary THC on allergic asthma compared to that of Cur in an animal model. METHODS: The anti-inflammatory effects of Cur and THC were evaluated in an ovalbumin-induced asthmatic mouse model. The nasal symptoms, pathological alterations of the lung tissues, oxidants and antioxidants, cytokine production, T cell subsets, and Th2-related signalling pathway activity were assessed. RESULTS: Both THC and Cur had beneficial effects on asthmatic mice with regard to nasal symptoms, pathological changes (eosinophils and mucus hyper-production), oxidative stress (malondialdehyde), cytokine production (IL-13), Th17 and cytotoxic T cell subsets, and Th2 signalling pathway (IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2-Notch1/Notch2 axis) activity. THC was more effective than Cur in suppressing tissue eosinophilia, mucus production, and IL-4Rα/Jak1/STAT6 pathway activity. Furthermore, only THC inhibited peripheral eosinophil levels, Th2 cytokines (IL-4 and IL-5), and Th2 cell subsets and enhanced an antioxidant enzyme (glutathione). CONCLUSION AND CLINICAL RELEVANCE: The above results demonstrated for the first time that THC was superior to Cur in modulating allergic asthmatic phenotypes, especially attenuating the Th2 response. THC might be a potentially effective agent for asthma treatment.

Learning to Diagnose Cirrhosis with Liver Capsule Guided Ultrasound Image Classification.

This paper proposes a computer-aided cirrhosis diagnosis system to diagnose cirrhosis based on ultrasound images. We first propose a method to extract a liver capsule on an ultrasound image, then, based on the extracted liver capsule, we fine-tune a deep convolutional neural network (CNN) model to extract features from the image patches cropped around the liver capsules. Finally, a trained support vector machine (SVM) classifier is applied to classify the sample into normal or abnormal cases. Experimental results show that the proposed method can effectively extract the liver capsules and accurately classify the ultrasound images.

An effective and robust method for tracking multiple fish in video image based on fish head detection.

BACKGROUND: Fish tracking is an important step for video based analysis of fish behavior. Due to severe body deformation and mutual occlusion of multiple swimming fish, accurate and robust fish tracking from video image sequence is a highly challenging problem. The current tracking methods based on motion information are not accurate and robust enough to track the waving body and handle occlusion. In order to better overcome these problems, we propose a multiple fish tracking method based on fish head detection. RESULTS: The shape and gray scale characteristics of the fish image are employed to locate the fish head position. For each detected fish head, we utilize the gray distribution of the head region to estimate the fish head direction. Both the position and direction information from fish detection are then combined to build a cost function of fish swimming. Based on the cost function, global optimization method can be applied to associate the target between consecutive frames. Results show that our method can accurately detect the position and direction information of fish head, and has a good tracking performance for dozens of fish. CONCLUSION: The proposed method can successfully obtain the motion trajectories for dozens of fish so as to provide more precise data to accommodate systematic analysis of fish behavior.

[Mechanisms Involved in the Inhibition of Melanin Synthesis by Bushen Quban Granule].

Objective To observe the molecular mechanism of Bushen Quban Granule (BQG) for inhibiting the synthesis of intracellular melanin. Methods Twenty SPF grade female SD rats were di- vided into four groups by completely randomized method, i.e., the control group (fed with normal saline) , high, middle, and low dose BQG groups (administered with BQG at 4. 8, 2. 4, 1. 2 g/kg by gastrogavage, equivalent to 24, 12, and 6 times clinical doses, respectively, twice per day for 3 days in total) , 5 in each group. Drug containing serum was collected. Expressions of melanocortin 1 receptor (MC1 R) , mi- crophthalmia-associated transcription factor ( MITF) , tyrosinase ( TYP) , tyrosinase-related protein I (TYRP1) , and tyrosinase-related protein 2 (TYRP2) at the mRNA level were detected by RT-PCR. Ex- pressions of phosphorylated-extracellular regulated MAP kinasel/2 (p-ERK) , TYP, TYRP1 and TYRP2 at the protein level were detected by Western blot. Intracellular melanin contents were determined by NaOH dissolving method. Activities of tyrosinase were determined by Dopa pigment method, and the cell viability was detected by MTT. Results Compared with the control group, expressions of MC1R, MITF, TYP, TYRP1 and TYRP2 at the mRNA level were down-regulated (P <0. 05), and those of TYP, TYRP1 and TYRP2 at the protein level were also down-regulated (P <0. 05), intracellular contents of melanin and the activity of tyrosinase decreased (P <0. 05) , but the level of p-ERK and the proliferation of cells increased in each medicated group (P <0. 05). When ERK was inhibited by its inhibitor PD98059, there was no sta- tistical difference in expressions of MC1 R or MITF at the mRNA level among all medicated groups (P > 0. 05). Compared with the control group, mRNA expressions of TYP, TYRP1 and TYRP2 decreased in the high dose BQG group (P <0. 05), but with no significant difference in protein expressions of p-ERK, TYP, TYRP1 and TYRP2 (P >0. 05). There was no statistical difference in the content of melanin, the activity of TYP, or the proliferation of cells between the control group and the high dose BQG group (P >0. 05). Con- clusion BQG could inhibit the synthesis of intracellular melanin through up-regulating p-ERK to inhibit the expression of tyrosinase and its related proteins.

Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men--the role of gut microbiota composition: study protocol for the AELC randomized controlled trial.

BACKGROUND: Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with an unhealthy lifestyle and pose extremely high costs to the healthcare system. In this study, we aim to explore whether individualized aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota composition and other post-interventional effects. METHODS/DESIGN: A 6-month randomized intervention with 6-month follow-up is conducted from January 2013 to December 2015. The target sample size for intervention is 200 postmenopausal women and middle-aged men aged 50-65 year-old with pre-diabetes and NAFLD. The qualified subjects are randomized into 4 groups with 50 subjects in each group: 1 = AEx, 2 = LCh, 3 = AEx + LCh, and 4 = control. In addition, two age-matched reference groups (5 = pre-diabetes without NAFLD (n = 50) and 6 = Healthy without pre-diabetes or NAFLD (n = 50)) are included. The exercise program consists of progressive and variable aerobic exercise (intensity of 60 to 75% of initial fitness level, 3-5 times/week and 30-60 min/time). The diet program includes dietary consultation plus supplementation with a special lunch meal (40% of total energy intake/day) which aims to reduce the amount of carbohydrate consumption (30%). The control and reference groups are advised to maintain their habitual habits during the intervention. The primary outcome measures are HFC, serum metabolomics and gut microbiota composition. The secondary outcome measures include body composition and cytokines. In addition, socio-psychological aspects, social support, physical activity and diet will be performed by means of questionnaire and interview. DISCUSSION: Specific individualized exercise and diet intervention in this study offers a more efficient approach for liver fat reduction and diabetes prevention via modification of gut microbiota composition. Besides, the study explores the importance of incorporating fitness assessment and exercise in the management of patients with pre-diabetes and fatty liver disorders. If our program is shown to be effective, it will open new strategies to combat these chronic diseases. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN42622771.

Effects of lifestyle intervention and meal replacement on glycaemic and body-weight control in Chinese subjects with impaired glucose regulation: a 1-year randomised controlled trial.

The purpose of the present study was to evaluate the impact of a lifestyle intervention programme, combined with a daily low-glycaemic index meal replacement, on body-weight and glycaemic control in subjects with impaired glucose regulation (IGR). Subjects with IGR were randomly assigned to an intervention group (n 46) and a control group (n 42). Both groups received health counselling at baseline. The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study, and follow-up visits performed monthly until the end of the 1-year study. Outcome measurements included changes in plasma glucose, glycated Hb (HbA1c), plasma lipids, body weight, blood pressure and body composition (such as body fat mass and visceral fat area). The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group (-1·8 (SEM 0·35) v. -0·6 (SEM 0·40) 2·5 kg, P<0·05). The 2 h plasma glucose concentration decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group (P<0·05) compared with their baseline, respectively. A 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose (P<0·01). The incidence of normal glucose regulation (NGR) in the two groups was significantly different (P=0·001). In conclusion, the combination of regular contact, lifestyle advice and meal replacement is beneficial in promoting IGR to NGR.

Development of an innovative minimally invasive primate spinal cord injury model: A case report.

Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.

Large deformation measurement using digital image correlation: a fully automated approach.

In digital image correlation, the iterative spatial domain cross-correlation algorithm is considered as a gold standard for matching the corresponding points in two images, but requires an accurate initial guess of the deformation parameters to converge correctly and rapidly. In this work, we present a fully automated method to accurately initialize all points of interest for the deformed images in the presence of large rotation and/or heterogeneous deformation. First, a robust computer vision technique is adopted to match feature points detected in reference and deformed images. The deformation parameters of the seed point are initialized from the affine transform, which is fitted to the matched feature points around it. Subsequently, the refined parameters are automatically transferred to adjacent points using a modified quality-guided initial guess propagation scheme. The proposed method not only ensures a rapid and correct convergence of the nonlinear optimization algorithm by providing a complete and accurate initial guess of deformation for each measurement point, but also effectively deals with deformed images with relatively large rotation and/or heterogeneous deformation. Tests on both simulated speckle images and real-world foam compression experiment verify the effectiveness and robustness of the proposed method.

Automated 3D trajectory measuring of large numbers of moving particles.

Complex dynamics of natural particle systems, such as insect swarms, bird flocks, fish schools, has attracted great attention of scientists for years. Measuring 3D trajectory of each individual in a group is vital for quantitative study of their dynamic properties, yet such empirical data is rare mainly due to the challenges of maintaining the identities of large numbers of individuals with similar visual features and frequent occlusions. We here present an automatic and efficient algorithm to track 3D motion trajectories of large numbers of moving particles using two video cameras. Our method solves this problem by formulating it as three linear assignment problems (LAP). For each video sequence, the first LAP obtains 2D tracks of moving targets and is able to maintain target identities in the presence of occlusions; the second one matches the visually similar targets across two views via a novel technique named maximum epipolar co-motion length (MECL), which is not only able to effectively reduce matching ambiguity but also further diminish the influence of frequent occlusions; the last one links 3D track segments into complete trajectories via computing a globally optimal assignment based on temporal and kinematic cues. Experiment results on simulated particle swarms with various particle densities validated the accuracy and robustness of the proposed method. As real-world case, our method successfully acquired 3D flight paths of fruit fly (Drosophila melanogaster) group comprising hundreds of freely flying individuals.

A nanozyme-linked immunosorbent assay based on metal-organic frameworks (MOFs) for sensitive detection of aflatoxin B1.

In order to avoid the occurrence of false positives and false negatives caused by conventional enzyme-linked immunosorbent assay (ELISA), we established a novel indirect competitive MOF-linked immunosorbent assay (MOFLISA) method for the high throughput and high sensitive detection of aflatoxin B1. This method replaces the natural enzyme with functional MOFs to catalyze a chromogenic system. As a result, the limit of detection (LOD) of the MOFLISA method was 0.009 ng·mL-1 with a linear working range from 0.01 to 20 ng·mL-1. The developed MOFLISA method for AFB1 has a 20-fold improved LOD value compared with the conventional ELISA. The recoveries and relative standard deviations (RSD) ranged from 86.41 to 99.74% and 2.38-9.04%, respectively. The results demonstrate that the recovery rate and accuracy of this detection method is better than that of conventional ELISA, reducing risks offalsepositive andfalsenegativeresults.

Wnt/ß-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients.

Chronic graft-versus-host disease (cGVHD) is the main cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mesenchymal stem cells (MSCs) in bone marrow (BM) remain unclear in the pathophysiology of cGVHD. In this study, we analyzed BM-MSCs from 66 patients after allo-HSCT, including 33 with active cGVHD and 33 without cGVHD. BM-MSCs showed similar morphology, frequency, phenotype, and proliferation in patients with or without cGVHD. MSCs from the active cGVHD group showed a decreased apoptosis rate (P < 0.01). Osteogenic capacity was increased while adipogenic capacity was decreased in the active cGVHD MSCs compared with no-cGVHD MSCs. The expressions of osteogenic gene RUNX2 and COL1A1 were higher (P < 0.001) while adipogenic gene PPAR-γ and FABP4 were lower (P < 0.001) in the active cGVHD MSCs than no-cGVHD MSCs. These changes were associated with the severity of cGVHD (P < 0.0001; r = 0.534, r = 0.476, r = -0.796, and r = -0.747, respectively in RUNX2, COL1A1, PPAR-γ, and FABP4). The expression of Wnt/ß-catenin pathway ligand Wnt3a was increased in cGVHD-MSCs. The dysfunction of cGVHD-MSCs could be reversed by Dickkopf related protein 1(DKK1) to inhibit the binding of Wnt3a. In summary, the differentiation of BM-MSCs was abnormal in active cGVHD, and its underlying mechanism is the upregulated of Wnt3a through Wnt/ß-catenin signaling pathway of MSCs.

Current advances in Phellinus sensu lato: medicinal species, functions, metabolites and mechanisms.

Twenty-six species of Phellinus sensu lato, reported as medicinal mushrooms, are enumerated in this review. The species' names were checked and revised according to contemporary taxonomy and the latest version of the International Code of Botanical Nomenclature (Vienna Code); two misapplied names of Phellinus baumii Pilát and Phellinus himalayensis Y.C. Dai in previous reports are also discussed. Of the 20 types of medicinal functions, the most shared functions are antitumor and improving immunity, both of which may be viewed as the basal functions of Phellinus s. l. In addition, alleviating septic shock, anti-inflammatory, and antioxidation are also a routine functions mentioned often. The main medicinal metabolites, including several kinds of polysaccharides and polyphenols, are introduced. Different methods and conditions could purify various polysaccharides with difference in activity level even from the same species, while all polyphenols are hispidin and its derivatives in general. Three aspects of mechanism contribute to antitumor activities of polysaccharides: (1) promoting an immune response, (2) inducing cell apoptosis, and (3) inhibiting metastasis. Other general mechanisms of the metabolites in antioxidant activity, and in treating diabetes, as well as complications are summarized. We also elaborate on potential scientific strategies for obtaining the medicinal metabolites from Phellinus s. l., such as artificial cultivation, the discoveries of more species with medicinal functions, the utilization of species growing quickly, and the optimization of culture conditions and media supplements in fermentation.

microRNA-9 and -29a regulate the progression of diabetic peripheral neuropathy via ISL1-mediated sonic hedgehog signaling pathway.

In this study, we tested the hypothesis that overexpression of miR-9 and miR-29a may contribute to DPN development and progression. We performed a meta-analysis of miR expression profile studies in human diabetes mellitus (DM) and the data suggested that miR-9 and miR-29a were highly expressed in patients with DM, which was further verified in serum samples collected from 30 patients diagnosed as DM. Besides, ISL1 was confirmed to be a target gene of miR-9 and miR-29a. Lentivirus-mediated forced expression of insulin gene enhancer binding protein-1 (ISL1) activated the sonic hedgehog (SHH) signaling pathway, increased motor nerve conduction velocity and threshold of nociception, and modulated expression of neurotrophic factors in sciatic nerves in rats with DM developed by intraperitoneal injection of 0.45% streptozotocin, suggesting that ISL1 could delay DM progression and promote neural regeneration and repair after sciatic nerve damage. However, lentivirus-mediated forced expression of miR-9 or miR-29a exacerbated DM and antagonized the beneficial effect of ISL1 on DPN. Collectively, this study revealed potential roles of miR-9 and miR-29a as contributors to DPN development through the SHH signaling pathway by binding to ISL1. Additionally, the results provided an experimental basis for the targeted intervention treatment of miR-9 and miR-29a.

ε3/4 genotype of the apolipoprotein E is associated with higher risk of Alzheimer's disease in patients with type 2 diabetes mellitus.

As a progressive and chronic disease, type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia with rising prevalence worldwide. The ε4 allele of the apolipoprotein E (ApoE) gene may be risk factor of severe peripheral neuropathy in T2DM patients. The association of ApoE polymorphism and Alzheimer's disease (AD) in T2DM patients remains largely unknown. Totally 156 T2DM patients with AD and 145 T2DM patients were included. The genotypes and allele frequency of ApoE were analyzed to explore the role of ApoE in AD in T2DM patients. The levels of total cholesterol (TC), triglyeride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were detected to further investigate mechanism of ApoE. Genotype frequency ratio of genotype ε3/4, ε4/4 and allele ε4 among the T2DM patients with AD was obviously increased. The TC, TG and LDL-C levels of T2DM patients with ε3/4 genotype were higher than those with ε3/3 or ε2/3 genotype and the ε3/4 genotype, while the HDL-C level was on the contrary, suggesting that ε3/4 genotype elevated blood lipid levels in T2DM patients with AD, thus increasing the risk of AD in T2DM patients. ApoE polymorphism was associated with AD in T2DM patients. ApoE ε3/4 genotype was possibly to serve as a risk factor for AD in T2DM patients by enhancing the blood lipid levels.

The nearest neighbor algorithm of local probability centers.

When classes are nonseparable or overlapping, training samples in a local neighborhood may come from different classes. In this situation, the samples with different class labels may be comparable in the neighborhood of query. As a consequence, the conventional nearest neighbor classifier, such as kappa-nearest neighbor scheme, may produce a wrong prediction. To address this issue, in this paper, we propose a new classification method, which performs a classification task based on the local probabilistic centers of each class. This method works by reducing the number of negative contributing points, which are the known samples falling on the wrong side of the ideal decision boundary, in a training set and by restricting their influence regions. In classification, this method classifies the query sample by using two measures of which one is the distance between the query and the local categorical probability centers, and the other is the computed posterior probability of the query. Although both measures are effective, the experiments show that the second one achieves the smaller classification error. Meanwhile, the theoretical analyses of the suggested methods are investigated, and some experiments are conducted on the basis of both constructed and real datasets. The investigation results show that this method substantially improves the classification performance of the nearest neighbor algorithm.