| Objective To understand the history of dry eye research by combing the literature on dry eye research in the Web of science database,summarized the syndrome distribution law of dry eye on traditional Chinese medicine literature and the potential association rules between symptom combinations,verified the regularity of the excavation,explored the association rules between the combination on clinical symptoms of dry eye and the condition of ocular signs/refractive,and quantified it in the form of maps;then screened for differential metabolites and related metabolic pathways in plasma and tear samples from people with yin deficiency of liver and kidney.Methods 1.We searched the Web of science database on the basis of the dry eye English theme,then the literature database was established in 5 years as a time unit,and the Citespace 5.2.R1 software was used to analyze for the frequency of topic words,betweenness centrality,Citation/Frequency Burst,topical cluster analysis of the data.In order to clarify the evolution of its research history.2.Based on the pre-set search conditions,the four Chinese databases were searched separately.After the data was sorted out,a literature database on traditional Chinese medicine for dry eye research was constructed.Used the data mining software IBM SPSS Modeler14.1 to explore the possible association rules between related symptom combinations through association rule analysis.3.First,the subjects were divided into dry eye group and control group by Clinical epidemiological study.Each group collected 202 patients,Moreover,the base line between the two groups were comparable.And then collected the general condition,clinical indicators and refractive status of all subjects.In addition,the dry eye group also collected the TCM syndrome type,eye symptoms,systemic symptoms,tongue,pulse and other data of the subjects,and the association rule analysis method was used to compare relevance in the clinical indicators and refractive status between the two groups、association rules between different age groups and refractive status、association rules between clinical indicators and refractive status.Secondly,the prospective study of the dry eye group subjects,using the data mining software IBM SPSS Modeler14.1 to verify the distribution of syndromes and the correlation of symptoms and symptom combinations,and further explore the clinical symptoms on this basis.The association rules between combination,refractive status,eye signs,and clinical indicators are quantified by association rule graphs and tables.4.The plasma samples and tear samples were collected from the dry eyes on yin deficiency of liver and kidney group and the asymptomatic control group.After pretreatment,the gas chromatography and mass spectrometry were used,through principal component analysis,orthogonal partial least squares-discriminant analysis and other processes,differential metabolites were screened and hierarchically clustered to find differential metabolites and related metabolic pathways.Results 1.Research on the evolution of foreign literature:(1)1992-1996: The main research includes classification of dry eye,study of tear film,dry eye caused by Sjogren’s syndrome,etc.Key words cluster analysis found that the research at this stage mainly includes corneal defects,prospective studies,tear osmotic pressure and so on.(2)1997-2001: A new study on “lacrimal gland” has emerged.The betweenness centrality: The key nodes are “epithelial cells”,“inflammation” and “model”;cluster analysis of keywords includes changes in cytokine balance,chromatin changes,and conjunctival epithelial expression,clinical management.(3)2002-2006: The frequency distribution of keywords has added the theme of “epidemic disease” compared with the previous two stages.This period of research focused on the exploration of mechanisms such as mucin,and cluster analysis of keywords found such as dry syndrome,chronic dry eye,dry eye questionnaire.(4)2007-2011: There have been studies in situ keratomileusis;cluster analysis of keywords mainly includes functional vision,visual outcomes,etc.(5)2012-2016: Key researches include meibomian gland dysfunction,etc.Key words cluster analysis obtained anxiety,chronic dry eye,etc.2.Traditional Chinese Medicine’s Literature research on dry eye: The most common TCM syndromes of dry eye are yin deficiency of liver and kidney.The symptoms of ocular surface are dry,foreign body and fatigue.The main symptoms of ciliary muscle stimulation are photophobia,and the main symptoms of visual function are blurred vision.The main systemic symptoms were dry mouth and nose,dry mouth,red tongue and bruises on tongue,fat tongue and thin tongue coating.Among the top five pulse distributions,there are either single or both fine veins;There are 5 groups of association rules for ocular surface symptoms,3 groups of association rules for systemic symptoms,3 rules for association between ocular symptoms and systemic symptoms,and 3 groups for association rules between tongue,pulse and eye symptoms.3.Clinical study:(1)Comparison of observation indexes:(1)There was no significant difference in the tear meniscus height(TMH)between the two groups(t=0.092,P=0.927),indicating that the TMH could not be used as a key difference index;(2)The difference of tear break-up time(BUT)between the two groups was statistically significant(t=-23.239,P<0.001),indicating that BUT is a difference index between dry eye and healthy person;(3)The difference between the two groups of OSDI scores was statistically significant(t=-48.422,P<0.001),indicating that the OSDI score is a difference between dry eye and healthy people;(4)There was a statistically significant difference in Schirmer between the two groups(t=27.670,P<0.001),indicating that Schirmer is a differential indicator between dry eye and healthy people;(5)Comparison of red scan analysis: There was a statistically significant difference in conjunctival hyperemia between the two groups(t=-2.475,P=0.014).There was a statistically significant difference in ciliary congestion between the two groups(t=-2.687,P=0.008),the difference of nasal conjunctival hyperemia between the two groups,the difference was statistically significant(t=-2.619,P=0.009),the nasal ciliary congestion between the two groups,the difference was statistically significant(t=-2.546,P=0.011),indicating that eye red analysis is an important indicator for measuring dry eye and healthy people.(2)Distribution of refractive status: Among the refractive conditions of dry eye subjects,the far-sightedness(mild hyperopia)is regarded as the main,the main refractive status of the asymptomatic control group was mild astigmatism.(3)Comparison of association rules between the two groups of subjects: There are 2 and 3 association rules between different age groups and refractive status in different groups;Moreover,there were 5 and 12 association rules between the clinical indicators and the refractive status of the two groups.(4)Distribution of TCM syndrome types: The most common TCM syndrome type of dry eye refractive group is liver and kidney yin deficiency syndrome(64.9%).(5)Distribution of symptoms and symptom combinations: We got several eye symptoms.The visual symptoms are only “observation blurred”,and the ocular surface symptoms are “dry”.“pain” is the most common symptom of ciliary muscle stimulation;these can be used as the main symptom in the diagnosis of dry eye,and the proportion of the score should be increased as an item of the scale.(6)Distribution of tongue image: The tongue coating of the dry eye group is mainly “thin yellow moss”.The texture of the tongue is mainly “red tongue”,and the tongue shape is thinner.(7)Distribution of pulse: The pulse of patients in the dry eye group also has the most “pulse fine” and “pulse breakdown”,indicating that the pathological changes of yin deficiency are the most,and the main symptoms combine with tongue and pulse.(8)Analysis of association rules about dry eye patients: The association rule between the combination of eye symptoms and refractive status is 35;the association rule between TCM syndrome and refractive status is 6;The association rule between tongue image,pulse and refractive conditions is 7;the association rule between systemic symptom combination and refractive status is 14;the association rule between TCM syndrome and clinical indicators is 4;The association rule of ocular symptom combination and clinical indicators is 15;the association rule between systemic symptom combination,tongue image,pulse and clinical indicators is 10,and these association rules have important clinical significance for the correlation between our interpretation indicators.4.Compared with the asymptomatic control group,there were 12 kinds of metabolites and 3 kinds of related metabolic pathways in the two groups.After comparing the difference of tear metabolism between the two groups,7 kinds of metabolites were found to be significantly different,and 2 kinds of related metabolic pathways were found.Conclusions 1.Foreign literature research shows that although the content of dry eye research pays attention to functional vision and visual results,it ignores the refractive status of dry eye patients and provides an entry point for clinical research.2.Research on traditional Chinese medicine literature shows that dry eye TCM syndrome type has the most research on liver and kidney yin deficiency,which provides literature support on dry eye metabolomics of liver and kidney yin deficiency type.And these laws also lay the foundation for the construction of the entries about the TCM syndrome scale.3.The most common findings of refractive status in dry eye patients are mild hyperopia.The relationship between the elderly over 60 years old and mild hyperopia is the strongest.The effect of mild hyperopia on the dry eye is important.The pathological changes of ciliary muscle contraction during hyperopia are more pronounced.Most common type of TCM syndrome in dry eye refractive group is liver and kidney yin deficiency syndrome,which is the clinical basis of metabolomics research.The relationship between liver and kidney yin deficiency syndrome and mild hyperopia is the strongest,and it also indirectly indicates the refractive error of the crowd is more obvious in the liver and kidney yin deficiency syndrome,and the combination of symptoms is also the strongest associated with mild hyperopia,indicating that the relationship between mild hyperopia and systemic symptoms is more closely related;the combination of ocular symptoms and Schirmer shows a strong correlation,indicating that Can be used as a key indicator of abnormalities in each eye symptom combination.4.There were 12 and 7 different metabolites in plasma samples and tear samples between the two groups,indicating that they are potential biomarkers of liver and kidney yin deficiency dry eye.Ubiquinone and other terpenoids-sputum biosynthesis,tyrosine metabolism,steroid hormone biosynthesis pathway abnormalities may be the intrinsic mechanism of systemic symptoms of liver and kidney yin deficiency’s dry eye.Abnormal pentose phosphate pathway and purine metabolic pathway may be the key mechanism for the development of ocular symptoms in the liver and kidney.Methoxytyramine 2 and dimeric glycerol 1 are common metabolites in plasma differential metabolites and tear differential metabolites.It is inferred that these two substances may be differential metabolites in dry eye refractive abnormalities of yin deficiency of liver and kidney. |
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