| Treating winter diseases in summer is one of the therapies of TCM in the prevention and treatment of diseases, which rooted in Huangdi Neijing.Winter disease treated in summer embodies the whole view of correspondence between man and universe, the view of advance prevention disease attack, the concept of balance of Yin and Yang theory of cultivating Yang in spring and summer while cultivating Yin in autumn and winter. Meanwhile, it also embodies the view of health preservation of meridian and the view of mutual restraint and interdependent of five elements. Under the guidance of the theory,a variety of specific treatments are induced, which mostly reflects the concept of winter disease treated in summer by acupoint application in dog days.Acupoint application therapy of winter disease treated in summer is applied to prevent and control a variety of diseases, especially lung diseases which has obtained obvious curative effect.Asthma, a kind of immune allergic disease, characterized by airway chronic inflammation, airway hyperresponsiveness and reversible airway obstruction is participated by a variety of cells and cell components. At present, there are about 300 million asthma patients in the world, among which each year about 15 million people lose their labor ability. China has 20 million patients with asthma, and the prevalence is rising, brought a heavy burden to patients and society. So asthma, the chronic lung disease is considered as a significant danger to public health. Western medicine shows obvious advantages in the treating acute attack of asthma, but in controlling non-acute stage of asthma, it is not good at. Because of good curative effect,low cost, no obvious adverse reactions, and low rate of recurrence, winter disease treated in summer is accepted by the masses of asthma patients. Butnow the mechanism is not clear and the related research is less, so it’s hard to expound its mechanism from the whole level. Further research on depends on technology platform for interpretation of TCM theory, and the metabonomics technology provides a good starting point.Metabolomics, a new branch of systematic biology after the rise of genomics, transcription group and proteomics, is a technology by which researching metabolic network of living things system through metabolite map and their dynamic changes before and after stimulating the living things. It skips the complicated regulation of life entity, obtains final and integral results through analysis on metabolite. Therefore, it is a technology revealing dynamic changes of organism on the whole. Avoiding the defects of researching physiological and pathological changes by single or few indicators in the past, metabonomics has the features of gathering entirety, dynamic,comprehension, analysis in one methodology, so it is in conformity with the principle of wholism in TCM, and is suitable for research of TCM.With metabonomics technology, metabolites were analyzed pre-treatment,post-treatment and the winter after treatment of asthma patients with Fei-qi deficiency syndrome using acupoint application, in order to discover the small molecular metabolic markers of asthma patients with Fei-qi deficiency syndrome, and endogenous material basis of curative effect of acupoint application therapy of winter disease treated in summer. Taking small molecular metabolic markers as clue to investigate the mechanism of acupoint application therapy of winter disease treated in summer in preventing and treating asthma. By discussing the effect of acupoint application therapy of winter disease treated in summer in immunity, inflammation, neural regulation mechanism in patients with asthma, the mechanisms involved are explored in a macroscopic level, at the same time, the clinical curative effect were counterevidenced. All of the above will lay foundation for precision medicine and enhance the clinical efficacy.This paper mainly includes the theoretical, clinical and experimental three parts:Part one Theoretical Overview of Winter Disease Treated in SummerObjective: To study theoretical connotation of winter disease treated in summer and summarize its clinical application and mechanism on asthma treatment. To witness the feasibility of using the new technology in winter disease treated in summer theory in-depth, all-sided.Methods:According to the ancient and modern literature, the theoretical origin, clinical application, mechanism of asthma treatment and new research way of the winter disease treated in summer theory were discussed in detail.Results:The winter disease treated in summer has the rich theoretical connotation and good clinical curative effect, and was used widely. But the mechanism is not clear, need to be further explored with research methods that suitable for TCM.Part two Clinical Effect of Acupoint Application of Winter Disease Treated in Summer on Bronchial AsthmaObjective: To observe the clinical effect of acupoint application therapy of winter disease treated in summer on bronchial asthma.Methods:This research adopts the paired comparison. Fifty patients with asthma were recruited and given acupoint application therapy of winter disease treated in summer intervention. The integral of symptom and the times of attack were recorded pre-treatment and post-treatment. Meanwhile compare the quality of life score.Results:Compared with the patients of pre-treatment, clinical symptom scores were significantly reduced, and the time of recurrence of asthma reduced in patients of post-treatment, the difference was statistically significant(P<0.05), the total effective rate was 86%. The scores of asthma symptoms, the condition of limited activities, psychological function and self health care were increased to different extent, the difference was statistically significant(P<0.05). The score of reaction to stimulation was improved, but not significant(P>0.05).Part three Experimental Study on Mechanism of Acupoint Application of Winter Disease Treated in Summer on Bronchial AsthmaExperiment one Studies of Plasma Metabonomics in Patients with Fei-qi Deficiency Syndrome Bronchial AsthmaObjective: To find potential biomarkers using metabonomics methods to study plasma metabonomics in patients with Fei-qi deficiency syndrome bronchial asthma.Methods:Fifty cases of Fei-qi deficiency syndrome bronchial asthma were recruited as sick group; Fifty healthy volunteers were enrolled as control group. The blood was collected respectively from people in control group and sick group. The plasma metabolites were detected using high performance liquid chromatography-mass spectrometry(HPLC-MS), statistical data were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The original spectrum and data of plasma metabolites were compared between the two groups to explore the potential biomarkers.Results:The metabolic spectrum of sick group was significantly different with that in control group. Histamine, cysteine, homocysteine, glutamate,ornithine, choline, zinc, epinephrine, homocarnosine were inferred as possibly potential biomarkers of Fei-qi deficiency syndrome bronchial asthma.Histamine, choline, ornithine, homocysteine in sick group were in a rising trend, the others were in a downward trend.Experiment two Research on the Mechanism of Acupoint Application of Winter Disease Treated in Summer on Bronchial Asthma Based on MetabolomicsObjective: To find potential biomarkers, using metabonomics methods to discuss the mechanism of acupoint application therapy of winter disease treated in summer on bronchial asthma.Methods:Fifty cases of Fei-qi deficiency syndrome bronchial asthma were recruited as sick group, acupoint application therapy of winter disease treated in summer was given as intervention. The blood was collected respectively from patients of sick group pre-treatment and post-treatment and the winter. The plasma metabolites were detected using high performanceliquid chromatography-mass spectrometry(HPLC-MS), and statistical data was analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The original spectrum and data of plasma metabolites were compared among the three timings, and explore the potential biomarkers.Results:(1) The metabolic spectrum of post-treatment was significantly different with that in pre-treatment. Histamine, choline, cysteine,homocysteine, zinc, ornithine, adenine, acetoacetic acid, dopamine were inferred as possibly potential biomarkers to distinguish pre-treatment and post-treatment. Histamine, choline, ornithine, homocysteine acetoacetic acid,adenine in post-treatment were in a downward trend, the others were in a rising trend.(2) The metabolic spectrum of the winter after treatment was significantly different with that of pre-treatment. Choline, cysteine, zinc,ornithine, epinephrine, homocarnosine, homocysteine, dehydroascorbic acid,acetylcholine were inferred as possibly potential biomarkers to distinguish pre-treatment and the winter after treatment. Choline, ornithine, homocysteine,acetylcholine in the winter after treatment were in a downward trend, the others were in a rising trend.Experiment three Influence of Acupoint Application of Winter Disease Treated in Summer on Immunity, Inflammation and Neural Regulation Mechanism in Patients with Bronchial AsthmaObjective: To explore the mechanism of acupoint application of winter disease treated in summer on bronchial asthma in immunity, inflammation and neural regulation.Methods:Fifty cases of Fei-qi deficiency syndrome bronchial asthma were recruited as sick group, acupoint application therapy of winter disease treated in summer was given as intervention. Fifty healthy volunteers were enrolled as control group. The concentrations of serum immunoglobin A, G,E(Ig A, IgG, IgE), interferon-γ(INF-γ), interleukin-4(IL-4), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10) and vasoactive intestinal peptide(VIP),plasma substance P(SP) of healthy volunteers and patients with asthma pre-treatment and post-treatment and the winter were detected. The difference among healthy volunteers, pre-treatment, post-treatment and the winter are compared.Results:(1) immune globulin: Compared with control group, serum IgE level was increased obviously, serum Ig A, IgG levels were decreased obviously in asthma patients of pre-treatment and post-treatment and the winter after treatment, the difference was statistically significant(P<0.05).Compared with pre-treatment, asthma patients in post-treatment and the winter after treatment, serum IgE levels were decreased obviously, serum IgA, IgG levels increased obviously, the difference was statistically significant(P<0.05).(2) cytokines:Compared with control group, serum INF-γ, IL-10 levels were reduced obviously, serum TNF-α content increases in asthma patients’ pre-treatment and post-treatment and the winter after treatment, the difference was statistically significant(P<0.05); IL-4 level increased in pre-treatment and the winter after treatment(P<0.05), but levels increased in post-treatment, not significant(P>0.05). Compared with pre-treatment, serum INF-γ, IL-10 levels increased significantly, serum IL-4 levels significantly decreased in asthma patients of post-treatment and the winter after treatment, the difference was statistically significant(P<0.05); The TNF-α content is decreased, but there was no significant difference(P>0.05).(3) neurotransmitter: Compared with control group, plasma SP content increased obviously, VIP content decreased obviously in asthma patients of pre-treatment and post-treatment and the winter after treatment, the difference was statistically significant(P>0.05).Compared with pre-treatment, plasma SP content decreased obviously, VIP content increased obviously in asthma patients in post-treatment and the winter after treatment, the difference was statistically significant(P>0.05).Conclusion:1 At present, researches on mechanism of acupoint application of winter disease treated in summer on bronchial asthma is limited, and only focusing on one single function or few indicators at certain time in summer, rather thanstudying it as a whole. Metabonomics technology has advantages to explore mechanism of acupoint application of winter disease treated in summer on bronchial asthma further, which provides the possibility to study it as a whole.2 Acupoint application of winter disease treated in summer not only can improve the clinical symptoms, reduce frequency of attacks, but also can improve the quality of survival. The curative effect is affirmation. The observation provides a solid clinical support to study the mechanism.3 Endogenous substance changes of Fei-qi deficiency syndrome bronchial asthma patient may be related to choline metabolism, amino acid metabolism and energy metabolism, and also accompanied by abnormal changes of hormone, microelements and cytokines. While there may be abnormity of antioxidant stress, anti-apoptosis and ammonia transport, and the lack of vitamins.4 The mechanism of acupoint application of winter disease treated in summer on bronchial asthma may be related to adjusting the amino acid metabolism and energy metabolism, enhancing immune function, improving the body’s antioxidant stress and anti-apoptosis, regulating the cell signal and neurotransmitters, improving ammonia transport, regulating hormone levels.5 The mechanism of acupoint application of winter disease treated in summer on bronchial asthma in the summer after treatment with control cell signaling and inhibiting allergic for mechanism; winter is to regulate hormone levels and enhance the antioxidant capacity of special mechanism.6 Acupoint application of winter disease treated in summer can improve immune function and reduce inflammation reaction by regulating secretion of cytokine and release of neurotransmitter, leading to therapeutic effect in bronchial asthma.7 There are differences between the mechanisms in summer and winter timing periods in treating bronchial asthma with Acupoint application of winter disease treated in summer method, so the exploring the difference can be helpful for the overall explanation. |
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