[Ridit analysis of experimental data from animal models of yang deficiency induced by different doses of hydrocortisone].

OBJECTIVE: Hydrocortisone-induced yang-deficiency animal model has now become the generally accepted model of yang deficiency. However, assessing the most appropriate dose of hydrocortisone is a long-term challenge. For analyzing the modeling dose, the authors have built several kinds of yang-deficiency models induced by hydrocortisone at different doses, and analyzed the experimental data with various mathematical statistical methods. In order to discuss the effects of the modeling dose on the basis of previous research, the authors introduced Ridit analysis. METHODS: After categorizing 27 batches of experiments with four different doses (including 2.5, 3.75, 10 and 20 mg/kg), the data were standardized and the data type was changed to meet the needs of subsequent calculations. Then, by using Ridit analysis, the authors compared the variation of 19 biochemistry indexes involving nervous-endocrine system, immune system, metabolic system and the function of the liver and kidney, so as to analyze the similarities and differences of those yang-deficiency models mentioned above. The effects of modeling dose were then discussed. RESULTS: With regard to the overall state of the animal model, the difference between the models induced by different doses of hydrocortisone (2.5, 3.75, 10 and 20 mg/kg) showed no statistical significance, indicating that differences in hydrocortisone dose barely lead to significant changes in yang-deficiency models. For the trends of changing in different indexes, indexes had different performances when the doses differs: gonad indexes (estradiol and testosterone) showed better performance in 2.5 mg/kg group, immunological indexes (immunoglobulin M and immunoglobulin G) showed better performance in 3.75 mg/kg group and metabolic indexes (triglyceride and total cholesterol) showed better performance in 10 mg/kg group, etc. This indicates that the dose of hydrocortisone should be determined according to the research purposes. CONCLUSION: Ridit analysis can be used as an integration analysis method for animal models of yang deficiency induced by hydrocortisone at different doses.

[A mathematical model for re-analysis of the relationship between essence of syndromes in traditional Chinese medicine and clinical biochemical indicators based on the residual-split method and its application].

Studying the essence of syndromes (Zheng) in traditional Chinese medicine (TCM) is a fundamental challenge in basic theoretical research of TCM. The relationship between any given syndrome and biochemical indicators is one of the important aspects of the study. As the indexes selected in each study are specific to a particular Western medical disease diagnosis, and the disease factor is inevitably introduced into the study, the effect of disease factor on the index changes cannot be assessed effectively by traditional data processing methods. This is known as "the same syndrome with different reasons", which has resulted in confusion in TCM research. This study aimed at providing a mathematical tool to address this issue. Based on information theory and the residual-split method, the syndrome information, which was covered in the index variation, was quantitatively calculated in this paper as an independent part of the disease factor. A mathematical model capable of objectively assessing and statistically testing the effect of the syndrome factor on the index changes was established. Applying this model to literature data of studies on the relationship between cyclic nucleotides and yang-deficiency syndrome showed following results. First, the values of yang-deficiency syndrome information were negative for cyclic adenosine monophosphate (cAMP) while positive for cyclic guanosine monophosphate (cGMP) in all included literature. This indicated that the group of yang-deficiency syndrome was correlated with an obvious trend of reduced cAMP levels and increased cGMP levels. Second, the statistical test results of yang-deficiency syndrome information of the two indexes were different among the literature included. The quality of original data was considered as a possible reason. Third, the significant differences between the yang-deficiency group of a specific disease and the normal group may, in some cases, be caused by a disease factor rather than a syndrome factor. The mathematical model provided a reasonable mathematical tool for the analysis of disease factor and syndrome factor in clinical research of TCM, suggesting that the mathematical model may give rise to innovative ideas and methods in the study of syndromes.

[Study of biological performance of Chinese materia medica with either a cold or hot property based on the three-element mathematical analysis model].

OBJECTIVE: The properties of Chinese materia medica are believed to be the summarization of the effects of biological performance on the various body states. Systemic discussion of chemical-factor elements, body-condition elements, biological-performance elements and their interrelationships is needed for research into the properties of Chinese materia medica. Following the practical characteristics of Chinese medicine, the three-element mathematical model was formed by introducing some mathematical concepts and methods and was used to study the cold or hot property of Chinese medicine, and to investigate the difference in biological performances of the two properties. METHODS: By using the concept of different functionality of Chinese medicine on abnormal states and the idea of interaction in mathematics, the effects of chemical-factor elements and body-condition elements were normalized to the amount of biological performance which was represented by some important indicators. The three-element mathematical model was formed with scatter plots through four steps, including effect separation, intensity calculation, frequency statistics and relevance analysis. A comparison pharmacology experiment of administration of hot property medicines, Fuzi (Radix Aconiti Lateralis Preparata) and Rougui (Cortex Cinnamomi), and cold property medicines, Huangbai (Cortex Phellodendri) and Zhizi (Fructus Gardeniae) on normal and glucocorticoid-induced yang-deficiency and yin-deficiency states was designed. The results were analyzed by the mathematical model. The scatter plots were the main output of model analysis. The expression of cold property and hot property was able to be quantified by frequency distribution of biological indexes of administrations on yang-deficiency and yin-deficiency states in the "efficacy zone" and "toxicity zone" of the plots and by the relevance analysis. RESULTS: The ratios of biological indicator frequency in the "efficacy zone" of administrations on yang-deficiency state and yin-deficiency state were 7:3 for Fuzi, 3:3 for Rougui, 4:4 for Huangbai and 1:5 for Zhizi. The sums of the biological indicator frequency in the "toxicity zone" of administration on the two states were 4 for Fuzi, 0 for Rougui, 2 for Huangbai and 4 for Zhizi. The relevance analysis showed that the order from Fuzi, Rougui, Huangbai to Zhizi was proportional to the change from "be true of yang-deficiency state" to "be true of yin-deficiency state". The extent of the hot property decreased while that of the cold property increased in the order of Fuzi, Rougui, Huangbai and Zhizi. The stronger the efficacy of above medicines is, the more obvious the toxicity displayed. CONCLUSION: The three-element mathematical model employed in this study is effectively capable of explaining the different biological expressions between hot property medicines and cold property medicines. This suggests that it may provide a mathematical tool and theoretical basis for the modern interpretation of cold property and hot property of Chinese medicine, and provide new ideas for further studing into the essence of Chinese medicine property theory.

[A study of association rules in three-dimensional property-taste-effect data of Chinese herbal medicines based on Apriori algorithm].

The theory of four properties (Qi) and five tastes (Wei) is the core of the property theory of Chinese materia medica. It is known that Qi and Wei are associated with the pharmacological effects (Xiao) of herbs. This study took records of all 365 Chinese herbs in Shennong's Classic of Materia Medica (Shennong Ben Cao Jing) as the data resource and established a three-dimensional data cube, in the purpose of finding out and analyzing the frequent patterns and valued association rules of Qi, Wei and Xiao based on Apriori algorithm. The results of this study may give rise to innovative ideas and methods in research of traditional Chinese materia medica.

[Classification of 365 Chinese medicines in Shennong's Materia Medica Classic based on a semi-supervised incremental clustering method].

Evidence of the pharmacological activity of traditional Chinese medicine (TCM) provides the basis for clinical prescription. Study of the classification of Chinese medicines according to these activities is key to understanding the general active tendencies of medicinal prescriptions, exploring their material basis, investigating their properties and searching for their alternatives. Taking the herbal classic Shennong's Materia Medica Classic (Shennong Bencao Jing) for the data source, this paper studied the classification of Chinese medicines based on semi-supervised incremental clustering algorithm using "micro-cluster" concept in order to investigate the complex similarity among Chinese medicines. The results showed that 253 Chinese medicines were reasonably classified into 14 types, such as invigoration, clearing heat, diuresis, dredging blockages in the channels, treating gynecological conditions and treating strange diseases caused by ghosts. The results also showed that the other 112 Chinese medicines were classified into 112 individual types and the same high similarity to different known types was the main reason for this. The semi-supervised incremental clustering algorithm employed in the study had a high quality and a good development for clustering which is suitable for classification of Chinese medicines. This study illustrated the diversity of Chinese medicines and their complex similarities, thus aiming to provide innovative ideas and methods for related research.

[Mathematical analysis of characteristics of glucocorticoid-induced yang deficiency or yin deficiency syndrome in animal models based on information entropy theory].

OBJECTIVE: Based on information entropy theory, this study analyzes the experimental indicators of glucocorticoid-induced traditional Chinese medicine yang deficiency or yin deficiency syndrome in animal models, thus laying the foundation of defining and interpreting the model state. METHODS: Data of biochemical indicators from 24 groups of animal models with different modeling conditions (type of modeling agent, dosage of modeling agent and modeling time) were collected. Information gain values for three study objects (type of modeling agent, dosage of modeling agent and modeling time) were calculated respectively after standardization, and then characteristics of yang deficiency or yin deficiency syndrome models were interpreted with these values and ranking map. RESULTS: Greatest information gain values of most indicators were got when the study object was the type of modeling agent, which is the most important factor in the differentiation of model state. With this study object, triglyceride (TG), total cholesterol (TC), total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and corticosteroid (CS) got larger information gain values than testosterone (T), lactic dehydrogenase (LDH), and cyclic adenosine monophosphate (cAMP). This indicated that the former seven indicators may be significantly different between the two animal models induced by hydrocortisone and dexamethasone, respectively. In the study of the modeling time, AST may be affected more than others. In the study of the dosage of modeling agent, TC and ALB may be affected more in the model of hydrocortisone and no indicators were significantly affected by the dosage of modeling agent in the dexamethasone model. CONCLUSION: Mathematical method based on information entropy theory allows researchers to analyze experimental data in several experiments at the same time and to interpret the trend and stability of indicators. Based on this study and by analyzing the impacts of different modeling conditions on the indicators, elucidations of the characteristics of glucocorticoid-induced yang deficiency or yin deficiency syndrome in animal models and some biochemical indicators for model comparison are in need.

[Mathematical analysis of the relationship between yang deficiency syndrome in traditional Chinese medicine and its objective indicators in clinical literature].

OBJECTIVE: The primary aim of this research is to systematically sort out and analyze available documents for yang deficiency syndrome in traditional Chinese medicine, providing innovative ideas and methods for statistical study of yang deficiency syndrome. METHODS: Based on the China National Knowledge Internet (CNKI) and Chongqing VIP databases, using "yang deficiency", "deficiency cold", and "patient" as keywords, we searched literature of clinical researches and used "ratio-comparison" and "integration-comparison" to analyze objective data after data preprocessing. Relative importance value of physiological and biochemical parameters were reflected by P value calculated by ratio-comparison or Q value by integration-comparison. RESULTS: With calculation of relative importance values of clinical indicators among various systems, we got the ranking of relative importance of different indexes. Triiodothyronine and urine 17-hydroxycorticosteroid of endocrine system, immunoglobulin A of immune system, and the ratio of cyclic adenosine monophosphate to cyclic guanosine monophosphate, which had great |P| (or |Q|) values and negative P (or Q) values, had a clearly lower level in yang deficiency patients than in the control; hemorheological indicators such as plasma viscosity, whole blood reduced viscosity and erythrocyte electrophoresis time had small |P| (or |Q|) values. These indicators, however, showed less importance for reflecting yang deficiency. CONCLUSION: Ratio-comparison method and integration-comparison method employed in this study have merits of efficiency and robustness. After detailed compiling and mining of all available data, we have made reasonable advice on the most relevant index of yang deficiency for further study of the essence of this syndrome.