The Research Based On Unsupervised Data Mining Technology Stroke Medication Rules And Discovery Of Prescription

Objective:In this study,we collected widely literature about treatment ofancient and modern stroke,applied the methods of modern computertechnology and statistics of combining, by the establishment of stroke diseaseprescription database,researched by using frequency,charts and othermathematical analysis methods,summarized and summed up the ancientphysicians on the stroke of the permit general awareness of the treatment oflaw and medicine characteristics and on the basis of the analysis of strokeprescription drug law, applied the unsupervised data mining technology toexcavate new prescriptions of stroke common syndromes and then used theexperiment to verify the validity,and opened new avenues for the discovery ofnew stroke compound medicines.Through the study to establish a compoundChinese medicine research and development mode about combination of datamining and the Chinese Medical Literature Analysis.Methods:1The study on ancient and modern literature of stroke medication rules1.1Established the stroke literature databasewe collected widely literature about treatment of ancient and modernstroke,sorted out in line with the literature included in the standard literaturerecords of855cases,normalized their symptoms,such as traditional Chinesemedicine name,collated and entered data in Epidata3.1software andtransformed into the SPSS18.0database with requirements of data mining andstatistical analysis, and then proceed to the next step database analysis.1.2The study on each historical period stroke medication rulesApplied the computer statistical software the SPSS18.0with frequencyanalysis method to comparative analysis on the stroke drug frequency of use,drug genus percentage,thus add up high frequency drug and high utilization drug genus percentage, and then infer the disease medication rules anddominant trend in the different historical period. Used the horizontal bar chartanalysis method to compare lateral various drugs flavor number and thepercentage of all drugs the percentage in the same dynasty, analyzed brieflystroke medication rules in same period;to compare vertical commonly usedclass of drugs of different dynasties to grasp stroke medication rules in history.2The research Based on unsupervised data mining technology stroke newdiscovery of prescriptionFrom855prescription stroke literature total database screenedrespectively syndrome of qi deficiency and blood stasis,syndrome ofobstruction of collateral due to wind-phlegm, syndrome of internal block ofphlegm-heat,syndrome of yin deficiency liver wind four syndromeprescription.Respectively entered each syndrome prescription to SPSS18.0software and processed data by the Institute of Automation, Chinese Academyof Sciences,Dr. Chen Jianxin designed unsupervised pattern discoveryanalysis software.Analyzed drug correlation by improved mutual information,entropy clustering method of complex systems,respectively obtained eachsyndrome commonly used drug pair and combination of core,assembledempirically drug pair and combination of core,obtained3new discovery ofprescription of each syndrome,and Traditional Chinese Medicine experts byresearching and discussing, identified new prescription in line with the clinicaltreatment of stroke each syndrome compatible law.3Based on unsupervised data mining technology stroke of syndrome ofqi deficiency and blood stasis new prescription—The effects of Shenlo-nghuoxuefang on experimental cerebral ischemia in rats neurological behavior, brain infarct area and the morphologyFocal cerebral ischemia model was developed with Male and female half SD rats of health clean grade. The animals were randomly divided into five groups: the sham group,the model group, Shenlonghuoxuefang high-dose (3.424g/kg d)group,low-dose(1.712g/kg d)group and the nimo-dipine (10mg/kg d) group. Using FeCl3patching a side of the middle c erebral artery established the model of focal cerebral ischemia. Sham group was only pushed aside meninges,not patching FeCl3.All groups wereirrigated before rats modeling7d, besides sham group and model groupwere gave isotonic Na chloride,Then each group was divided into twotime points:6h and7d (n=6). Beam Walking Test, Muscle Strength Test and Wrong Step Test were used for neurological behavior grading.HEstaining was used to detect the histomorphological changes of brain tissue and TTC staining was used to calculate the proportion of cerebral infarction area After cerebral ischemia7d.4The effects of Shenlonghuoxuefang on experimental cerebral ischemia ratsin the permeability of BBB and the protection of the mechanism of actionGrouping and modeling equivalent to3.The levels of L-1β,IL-10,SO-D,MDA in serum were tested through taking blood from peritoneal cavity,separating serum after rats cerebral ischemia6h and7d;Evens Blue(EB) assay was used to detect the permeability of BBB after rats cerebralischemia6h;Transmission electron microscope was used to observe thediversification of BBB ultrastructure after rats cerebral ischemia6h and7d;S-P immunohistochemistry and RT-PCR assessments were used to detect the protein and mRNA distribution and expression levels of tight junction-associated protein ZO-1,occludin, and claudin-5in all rats brain tissue.Results:1The study on each historical period stroke medication rulesOn the basis of the stroke literature database using frequency analysis method derived:Tang and Song dynasties ago,67flavors high-frequency drugs,Among them,exterior-releasing medicinal,tonifying and replenishing medicinal,wind-dampness-dispelling medicinal were used most frequently;Jin and Yuan dynasties,52flavors high-frequency drugs,tonifying andreplenishing medicinal,resolve phlegm drug,exterior-releasing medicinal,liver-pacifying and wind-extinguishing medicinal were used most frequently;Ming and Qing dynasties,70flavors high-frequency drugs,Among them,to nifying and replenishing medicinal,exterior-releasing medicinal,resolve phlegm drug,liver-pacifying and wind-extinguishing medicinal were used most frequently;Near the modern era,47flavors high-frequency drugs,Among them,tonifying and replenishing medicinal,liver-pacifying and wind-extinguishing medicinal,resolve phlegm drug were used most frequently;In the total database,78flavors high-frequency drugs,Among them,tonifying and replenishing medicinal,exterior-releasing medicinal,resolve phlegm drug,liver-pacifying and wind-extinguishing medicinal,wind-dampness-dispelling medicinal,blood-activating and stasis-resolving medicinal,warm the interior medicinal,heat-clearing formula,qi-regulating medicinal,orifice-opening medicinal etc.10kinds of drugs were used higher frequently.Using bar chart analysis methods Horizontal compared with the thedynasties various types of drugs flavor number and the percentage of a-ll medicines percentage (results with the frequency analysis method);Longitudinal compared with different dynasties commonly used drug classes,exterior-releasing medicinal were used most frequently before Tang andSong dynasties,on the contrary, in near the modern era;Using frequencyof wind-dampness-dispelling medicinal descended with time;Tonifying and replenishing medicinal were used frequency over10%of all drug use in the period,the highest in Ming and Qing dynasties;Liver-pacifying and wind-extinguishing medicinal were used most frequently;using frequency of resolve phlegm drug rised with time;Blood-activating and stasis-resolving medicinal and orifice-opening medicinal were used frequency changes little in the treatment of stroke during each period.2The research Based on unsupervised data mining technology strokenew discovery of prescriptionFrom the total database of ancient and modern stroke literature screenedrespectively syndrome of qi deficiency and blood stasis,syndrome ofobstruction of collateral due to wind-phlegm, syndrome of internal block ofphlegm-heat,syndrome of yin deficiency liver wind four syndromeprescription.By analyzing277cases drugs of syndrome of qi deficiency and blood stasis,obtaining78flavors high-frequency drugs,applied respectivelyimproved mutual information method, entropy clustering method of complexsystems, obtaining44drug pair and61combination of core,assembledempirically drug pair and combination of core,obtained3new prescription thesyndrome(Shenlonghuoxuefang was inside);By analyzing213cases drugs ofsyndrome of obstruction of collateral due to wind-phlegm,obtaining53flavorshigh-frequency drugs,applied respectively the above method,obtaining26drugpair,19combination of core and3new prescription the syndrome;Byanalyzing128cases drugs of syndrome of internal block ofphlegm-heat,obtaining43flavors high-frequency drugs,applied respectivelythe above method, obtaining26drug pair,19combination of core and3newprescription the syndrome;By analyzing64cases drugs of syndrome of yindeficiency liver wind,obtaining28flavors high-frequency drugs,appliedrespectively the above method, obtaining20drug pair,19combination of coreand3new prescription the syndrome.3The effects of Shenlonghuoxuefang on experimental cerebral ischemiain rats neurological behavior, brain infarct area and the morphologyNeurological behavior scoring:after rats cerebral ischemia6h and7d,compared with the sham group, behavior performance of the model group rats,hindlimb motor coordination and integration capabilities, limb muscle strength,forelimbs placed function were poor(P＜0.01);compared with the model group,Shenlonghuoxuefang high-dose group significantly improved model rats offocal cerebral ischemia behavior scoring(P＜0.01),Shenlonghuoxuefanglow-dose group and nimodipine group weren't obvious improvement.Histomorphological changes:after rats cerebral ischemia6h and7d,compared with the sham group,brain tissue morphology of the model group rats injured seriously;compared with the model group, nerve cells ofischemic changes of Shenlonghuoxuefang high-dose group and nimodipine group was significantly reduced,Perivascular and nerve cells around space widening was significantly reduced,the necrotic cells numbers weresignificantly reduced.Shenlonghuoxuefang low-dose group ischemic chan ges wasn't significantly reduced.The changes of infarction area:after rats cerebral ischemia7d, comparedwith the sham group,the model group rats infarction area was significantlyincreased(P＜0.01);compared with the model group, Shenlonghuoxuefanghigh-dose group significantly reduced the infarct area of cerebral ischemia inrats(P＜0.01),Shenlonghuoxuefang low-dose group and nimodipine groupreduced the infarct area of cerebral ischemia in rats(P＜0.05).4The effects of Shenlonghuoxuefang on experimental cerebral ischemiarats in the permeability of BBB and the protection of the mechanism of actionThe test results of Serum IL-1βlevels:after rats cerebral ischemia6hand7d, compared with the sham group,the model group IL-1βcontent significantly increased(P＜0.05);compared with the model group, Shenlong-huoxuefang high-dose group IL-1βcontent significantly reduced(P＜0.05),Shenlonghuoxuefang low-dose group and nimodipine group weren't discriminating(P＞0.05).The test results of Serum IL-10levels:after rats cerebral ischemia6h and7d, compared with the sham group,the model group IL-10conten-t significantly reduced(P＜0.05);compared with the model group, Shenlonghuoxuefang high-dose group IL-10content significantly increased(P＜0.01),Shenlonghuoxuefang low-dose group and nimodipine group IL-10content significantly increased(P＜0.05).The test results of Serum SOD levels:after rats cerebral ischemia6h and7d, compared with the sham group,the model group SOD contentsignificantly reduced(P＜0.05,P＜0.01);compared with the model group,Shenlonghuoxuefang high-dose group and nimodipine group SOD contentsignificantly increased(P＜0.01),Shenlonghuoxuefang low-dose group SODcontent significantly increased(P＜0.05).The test results of Serum MDA levels:after rats cerebral ischemia6h and7d, compared with the sham group,the model group MDA conten-t significantly increased(P＜0.01);compared with the model group,Shenlonghuoxuefang high-dose group MDA content significantly reduced(P＜0.0 1),Shenlonghuoxuefang low-dose group and nimodipine group MDA content significantly reduced(P＜0.05).The test results of the permeability of BBB:after rats cerebral ischemia6h, compared with the sham group,the model group Evens Blue(EB)-OD value significantly increased(P＜0.05);compared with the model group,Shenlonghuoxuefang high-dose group and nimodipine group Evens Blue(EB) OD value significantly reduced(P＜0.05),Shenlonghuoxuefang low-dose group wasn't discriminating(P＞0.05).The changes of BBB ultrastructure by transmission electron microscopeto observe:after rats cerebral ischemia6h and7d, compared with the shamgroup,the model group BMECS injured seriously;compared with the modelgroup,each treatment group were improved,Shenlonghuoxuefang high-dosegroup,could be seen more complete BBB structure and couldn't be seensignificant opening TJ,capillaries surrounding was mildly edema.After ratscerebral ischemia6h,Shenlonghuoxuefang low-dose group,could be seen TJwith the state of semi-open,capillaries surrounding was moderatelyedema;after rats cerebral ischemia7d,could be seen TJ structureambiguous,capillaries surrounding was mildly edema. nimodipine group,afterrats cerebral ischemia6h,couldn't be seen significant opening TJ and could beseen membrane ambiguous,capillaries surrounding was mildly edema,afterrats cerebral ischemia7d,could be seen TJ with the state ofsemi-open,capillaries surrounding was mildly edema.The test results of the mRNA expression levels of tight junction-associated protein ZO-1,occludin, and claudin-5:after rats cerebral ischemia6h and7d, compared with the sham group,the model group mRNA expression levels of three protein was the lowest;after rats cerebral ischemia6h,compared with the model group,Shenlonghuoxuefang high-dose gro-up mRNA expression levels of three protein significantly increased,Shenlonghuoxuefang low-dose group and nimodipine group mRNA expressionlevels was equivalent,and lower than Shenlonghuoxuefang high-dose group.After rats cerebral ischemia7d,compared with the model group,each t reatment group mRNA expression levels of three protein increased,the mRNA expression levels of protein ZO-1of Shenlonghuoxuefang low-dosegroup, slightly higher than high-dose group.The mRNA expression levels of the other two proteins of Shenlonghuoxuefang high-dose group, slightly higher than low-dose group.The expression levels changes of tight junction-associated protein ZO-1, occludin, and claudin-5by immunohistochemistry assessment to detect:after rats cerebral ischemia6h and7d,compared with the sham group,the model group protein expression levels significantly reduced;comparedwith the model group,Shenlonghuoxuefang high-dose group,low-dose gr-oup,nimodipine group protein positive distribution was closely and coloring obviously,among them,Shenlonghuoxuefang high-dose group protein positive expressed most obviously,nimodipine group and Shenlonghuoxuefang low-dose group protein positive expressed more obviously.Conclusion:1Established the stroke literature database,excavated the treatment oflaw and medicine characteristics of each historical period stroke fromthem,and expanded its connotation,thus provided a theoretical and clinicalbasis for diagnosis and treatment of stroke.2Applied complex systems analysis methods to the stroke literaturemining,by excavating the potential law of drugs combination in thecombination of drugs,discovered new prescription in line with the clinicaltreatment of stroke different syndrome.3Verified experimental validation and discussed preliminary mechanismfor represented prescription by data mining,thus explored preliminarilydevelopment of new models and approach of chinese medical compoundformula.