Volumetric magnetic resonance imaging classification for Alzheimer’s disease based on kernel density estimation of local features

Background The classification of Alzheimer's disease (AD) from magnetic resonance imaging (MRI) has been challenged by lack of effective and reliable biomarkers due to inter-subject variability.This ar...     

A data structure and function classification based method to evaluate clustering models for gene expression data

Objective: To establish a systematic framework for selecting the best clustering algorithm and provide an evaluation method for clustering analyses of gene expression data. Metlaods: Based on data struc-ture (internal information) and function classification (external information), the evaluation of gene expres-sion data analyses were carried out by using 2 approaches. Firstly, to assess the predictive power of cluster-ing algorithms, Entropy was introduced to measure the consistency between the clustering results from differ-ent algorithms and the known and validated functional classifications. Secondly, a modified method of figureof merit (adjust_FOM) was used as internal assessment method. In this method, one clustering algorithm was used to analyze all data but one experimental condition, the remaining condition was used to assess the predictive power of the resulting clusters. This method was applied on 3 gene expression data sets (2 from the Lyer‘‘s Serum Data Sets, and 1 from the Ferea‘‘s Saccharomyces Cerevisiae Data Set). Results: A method based on entropy and figure of merit (FOM) was proposed to explore the results of the 3 data sets obtained by 6 different algorithms, SOM and Fuzzy clustering methods were confirmed to possess the highest ability to cluster. Conclusion: A method based on entropy is firstly brought forward to evaluate clustering analyses. Different results are attained in evaluating same data set due to different function classification. According to the curves of adjust-FOM and Entropy-FOM, SOM and Fuzzy clustering methods show the highest ability to cluster on the 3 data sets.     

基于流行排序算法的病毒性肝炎证候分类

Treatment determination based on syndrome differentiation is the key of Chinese medicine. A feasible way of improving the clinical therapy effectiveness is needed to correctly differentiate the syndrome classifications based on the clinical manifestations. In this paper, a novel data mining method based on manifold ranking （MR） is proposed to explore the relation between syndromes and symptoms for viral hepatitis. Since MR could take the symptom data with expert differentiation and the symptom data without expert differentiation into the task of syndrome classification, the clinical information used for modeling the syndrome features is greatly enlarged so as to improve the precise of syndrome classification. In addition, the proposed method of syndrome classification could also avoid two disadvantages in previous methods： linear relation of the clinical data and mutually exclusive symptoms among different syndromes. And it could help exploit the latent relation between syndromes and symptoms more effectively. Better performance of syndrome classification is able to be achieved according to the experimental results and the clinical experts.     

Integration of Chinese Medicine with Western Medicine Could Lead to Future Medicine: Molecular Module Medicine

The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drugdiscovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.     

血瘀证诊断标准：标准化模式识别的思考

Pattern identification(PI),also called Bian Zheng(辨证),syndrome differentiation,pattern diagnosis,or pattern classification,is the basic principle and the key concept of Chinese medicine(CM).The core of PI is CM syndrome,on which CM theory,therapeutic method,prescribing formula and the use of Chinese herbal medicine are basically based.PI,in fact,is another classification method anticipated to improve the clinical efficacy.How to make an exact PI seems to be very important for taking full advantage of PI in clinical practice.Therefore,the establishment of diagnostic criterion of pattern has been the prerequisite for the standardization of PI.In recent years,a lot of diagnostic criteria of different CM patterns have been formulated.Taking the diagnostic criteria for blood-stasis syndrome as a model,the methodologies and considerations in establishing a pattern diagnostic criterion were discussed in this paper,which might be of great reference value in future PI standardization research.     

Analysis of the Diagnostic Consistency of Chinese Medicine Specialists in Cardiovascular Disease Cases and Syndrome Identification Based on the Relevant Feature for Each Label Learning Method

Objective:To analyze the diagnostic consistency of Chinese medicine(CM) specialists in patients with cardiovascular disease and to study syndrome classification and identification based on the multi-label learning method.Methods:Using self-developed CM clinical scales to collect cases,inquiry information,complexity,tongue manifestation and pulse manifestation were assessed.The number of cases collected was 2,218.Firstly,each case was differentiated by two CM specialists according to the same diagnostic criteria.The consistency of the diagnosis based on Cohen’s Kappa coefficient was analyzed.Secondly,take the same diagnosis syndromes of two specialists as the results of the cases.According to injury information in the CM scale "yes" or "no" was assigned "1" or "0",and according to the syndrome type in each case "yes" or "no" was assigned "1" or "0".CM information data on cardiovascular disease cases were established.We studied CM syndrome classification and identification based on the relevant feature for each label(REAL) leaming method,and the diagnostic rate of the syndrome was studied using the REAL method when the number of features selected was 5,10,15,20,30,50,70,and 100,respectively.Results:The syndromes with good diagnostic consistency were Heart(Xin)-qi deficiency,Heart-yang deficiency,Heart-yin deficiency,phlegm,stagnation of blood and stagnation of qi.Syndromes with poor diagnostic consistency were heartblood deficiency and blood deficiency of Heart and Liver(Gan).The highest diagnostic rates using the REAL method were Heart-yang deficiency followed by Heart-qi deficiency.A different number of features,such as 5,10,15,20,30,40,50,70,and 100,respectively,were selected and the diagnostic accuracy based on five features showed the highest diagnostic accuracy.The top five features which had a strong correlation with the syndromes were in accordance with the CM theory.Conclnsions:CM syndrome differentiation is strongly subjective and it is difficult to obtain good diagnostic consistency.The REAL method fully considers the relationship between syndrome types and injury symptoms,and is suitable for the establishment of models for CM syndrome classification and identification.This method can probably provide the prerequisite for objectivity and standardization of CM differentiation.     

Methodology and Application for Health Risk Classification of Chemicals in Foods Based on Risk Matrix

The method has been developed to accurately identify the magnitude of health risks and provide scientific evidence for implementation of risk management in food safety.It combines two parameters including consequence and likelihood of adverse effects based on risk matrix.Score definitions and classification for the consequence and the likelihood of adverse effects are proposed.The risk score identifies the intersection of consequence and likelihood in risk matrix represents its health risk level with different colors:‘low',‘medium',‘high'.Its use in an actual case is shown.     

Bioactivities and Pharmaceutical Effects of 1-Aminocyclopro- panecarboxylic Acid

Objective The 1-aminocyclopropanecarboxylic acid (ACPC) is a natural micromolecule non-protein amino acid that exists only in plants. Despite the determination of its regulating effects on plants, several bioactivities and effects on animals or humans are still unclear. This review focuses the pharmaceutical effects,above all, the neuroprotective effects of ACPC on the cerebro- and cardiovascular system. Methods Two hundred and seventy nine studies were selected and identified from a total of 2457 references in Medline and Chemical Abstracts from 1957 to 2008. Only 38 articles on neuroprotective effects of ACPC from seven different countries qualified to be included in the analysis. Results ACPC has altogether following six general neuroprotective effects on the brain and nervous system: anti-neurotoxicity induced by NMDA, dynorphin-A, glutamate, and morphine; protection from cerebral neurological injury induced by ischemia; antidepressant and anxiolytic effects; anti-convulsion and -seizures and control of epilepsy; facilitation of spatial learning and memory; and the effect of reducing alcohol consumption. Conclusion ACPC has shown a variety of effects on plants and animals. The bioactivities and pharmaceutical effects on animals are of great significance to medical research and public health. Further clinical trials or epidemiological studies are needed to determine its effect in humans. Food intervention with ACPC-rich vegetables and fruits may be a suitable therapy for cerebro- and cardiovascular system diseases. Administration of trace exogenous ACPC could produce vegetables and fruits of rich endogenous ACPC.     

Analysis of TRPA1 antagonist,A-967079,in plasma using high-performance liquid chromatography tandem mass-spectrometry

The noxious effects from exposure to toxic inhalation hazards(TIHs,such as isocyanates,chlorine,etc.)are known to be triggered by the activation of transient receptor potential ankyrin 1(TRPA1)ion channel.Antagonists of TRPA1 have shown near complete attenuation of the noxious effects from TIH exposure.One of the TRPA1 antagonists,(1E,3E)-1-(4-fluorophenyl)-2-methyl-1-pentene-3-one oxime(A-967079),has shown impressive efficacy,high selectivity,high potency,and oral bioavailability.Although a vali-dated method to quantify A-967079 in biological matrices is vital for the further development of A-967079 as a therapeutic agent,no method for its analysis from any matrix is currently available.Hence,a rapid and simple HPLC-MS/MS method was developed and validated to quantify A-967079 in rabbit plasma.The method presented here features an excellent LOD of 25 nM and a wide linear range(0.05-200μM),with good accuracy and precision(100±10.5%and<14.2%relative standard deviation,respectively).The stability of A-967079 in plasma was excellent for most of the storage conditions evaluated.The method was successfully applied to determine A-967079 from treated animals and it may facilitate the development of this TRPA1 antagonist as a therapeutic agent against the noxious effects of TIH exposure.     

Issues on the selection of non-inferiority margin in clinical trials

Objective The determination of non-inferiority margin is an important and confusing issue which directly influences the acceptability of a new medication. We reviewed the published literature, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use （ICH） Guidelines and Committee for Proprietary Medicinal Products （CPMP） papers on the selection of non-inferiority margin and the corresponding statistical tests in clinical trials, in order to provide practical recommendations and suggestions for establishing reference criteria for the non-inferiority margin in China.
Data sources The literature on the selection of a non-inferiority margin and statistical tests was mainly extracted from relevant English articles on non-inferior clinical trials published from 1990 to 2007. The starting point （1990） was chosen due to lack of such papers published prior to 1990. This literature was searched via PubMed, Medline and Chinese Knowledge Information （CNKI）. ICH guidelines and CPMP papers were downloaded from their official websites. The keywords ＂clinical trial＂, ＂non-inferiority＂ and ＂non-inferiority margin＂ were used.
Study selection Forty-three original articles and critical reviews, ICH El0 guideline and CPMP papers were selected. Results The non-inferiority testing with treatment difference and ratio are commonly used, where the non-inferiority margin is determined with and without historical data. Traditionally, this margin is treated as a fixed value, while developed methods take the variation into account in the determination of this margin, on which the test depends is more convincing. The mixed margin consisting of a margin based on treatment difference and a margin based on treatment ratio can exactly control the type I error at the desirable level and obtain a better power. In this review, we also provide some recommendations and suggestions for the selection of the non-inferiority margin in the western countries and China.
Conclusions Besides the magnitude and variability of the standard control and placebo effects, the determination of the margin depends on other factors, such as, the safety profiles of the two comparative therapies, method of administration and product cost. Hence the margin should be made specifically for a certain case. Reference criteria for different medications should be given to avoid the arbitrary conclusion.     

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images

Objective: To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease(NAFLD) based on features of tongue images. Methods: Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, ...     

Image analysis on corneal opacity: A novel method to estimate postmortem interval in rabbits

Corneal opacity is one of the most commonly used parameters for estimating postmortem interval （PMI）. This paper proposes a new method to study the relationship between changes of corneal opacity and PMI by processing and analyzing cornea images. Corneal regions were extracted from images of rabbits＇ eyes and described by color-based and texture-based features, which could represent the changes of cornea at different PMI. A KNN classifier was used to reveal the association of image features and PMI. The result of the classification showed that the new method was reliable and effective.     

冠心病血瘀证：从现代医学视角理解

The medical community as a whole is attempting to start preventive therapy for coronary heartdisease （CHD） patients earlier in life. However, the main limitations of such interventions are drug resistanceand adverse reactions. Additionally, traditional biomarker discovery methods for CHD focus on the behavior ofindividual biomarkers regardless of their relevance. These limitations have led to attempting novel approachesto multi-dimensionally investigate CHD and identify safe and efficacious therapies for preventing CHD. Recently,the benefit of Chinese medicine （CM） in CHD has been proven by increasing clinical evidence. More importantly,linking CM theory with modern biomedicine may lead to new scientific discoveries. According to CM theory,all treatments for patients should be based on patients＇ syndromes. A recent epidemiological investigation hasdemonstrated that blood stasis syndrome （BSS） is the major syndrome type of CHD. BSS is a type of complexpathophysiological state characterized by decreased or impeded blood flow. Common clinical features ofBSS include a darkish complexion, scaly dry skin, and cyanosis of the lips and nails, a purple or dark tonguewith purple spots, a thready and hesitant pulse, and stabbing or pricking pain fixed in location accompaniedby tenderness, mass formation and ecchymosis or petechiae. The severity of BSS is significantly correlatedwith the complexity of coronary lesions and the degree of stenosis, and is an important factor affecting theoccurrence of restenosis after percutaneous coronary intervention. The mechanisms of BSS of CHD patientsshould be investigated from a modern medicine perspective. Although many studies have attempted toexplore the biomedical mechanisms of BSS of CHD, from hemorheological disorders to inflammation andimmune responses, the global picture of BSS of CHD is still unclear. In this article, the current status of studiesinvestigating the biomedical mechanisms of BSS of CHD and future perspectives are discussed.     

Ultrasonic studies of the effect of artemisia decoction on the volume and dynamics of gallbladder.

This paper deals with the ultrasonic studies of the effect of artemisia decoction (AD) on the volume and motion of gallbladder in 33 cases. Ultrasonic examination shows that AD intravenous infusion has remarkable effects on the contractility of gallbladder. There are 4 patterns of phasic changes in the motion of gallbladder and an increase in frequency of its contraction and relaxation. AD has also certain contraction effects on the gallbladders which can not contract after a fatty meal. The above findings indicate that AD is a good choleretic and has a definite regulating effect on the motility of the gallbladder. The clinical use of AD is conducive to bile flow, stone expelling, inhibiting the deposition of bile solids and reducing the possibility of stone formation.

     

Effects and mechanisms of actions of Chinese herbal medicines for asthma

Asthma is a chronic inflammatory disorder of airways that affects approximately 300 million adults and children worldwide.Most therapy currently uses bronchodilators and corticosteroids.Systemic side effects from chronic use of these drugs are concern.Chinese medicine(CM)has a long history of human use in China and other Asian countries and well received by the patients.But as one component of Western integrative medicine(WIM),it is required that CM use is supported by scientific evidence.On the other hand,there are also suggestions that Western standardized medicine should consider personalized practice.In recent years there have been an increasing studies to narrow the gap between CM,the personalized medicine and Western medicine,evidence based medicine.This communication reviews several CM studies published in the English language in details by reviewing the effects and mechanisms of actions on asthma from clinic and experimental studies. Chinese herbal medicines exhibit broad actions on multiple asthma pathologic mechanisms.These mechanisms may involve antiinflammatory and immunomodulatory effects,inhibiting airway remodeling and normalization of hypothalamus,pituitary and adrenal(HPA)-axis disturbances.However,the mechanisms of actions of Chinese herbal medicines for asthma are not fully understood.More controlled clinical studies are warranted and some anti-asthma CM may be proved to be effective when used as monotherapy or complementary asthma therapies.     

Prediction of response of collagen-induced arthritis rats to methotrexate: An 1H-NMR-based urine metabolomic analysis

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance (1H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R2=0.812, Q2=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.     

Application of Benchmark Dose （BMD） in Estimating Biological Exposure Limit （BEL） to Cadmium

Objective To estimate the biological exposure limit （BEL） using benchmark dose （BMD） based on two sets of data from occupational epidemiology. Methods Cadmium-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 D2-microgloburin （B2M）, N-acetyl-D-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. Results The 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, NAG9 and ALB） and exposure biomarker （UCd）. BEL value was 5 μg/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 μg/g creafinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected. Conclusion BMD can be used in estimating the biological exposure limit （BEL）. UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.