| Purpose:Through data mining studies,Randomized Controlled Trial studies and Real World studies,this paper explores the medication rules of Traditional Chinese Medicine in the treatment of Blood-Stasis headache,evaluates the effectiveness and safety of Xuefu Zhuyu oral liquid in the treatment of patients with Tension Headache syndrome of Qi-Stagnation and Blood-Stasis,and compares,analyzes and evaluates the influence of Xuefu Zhuyu oral liquid on the changes of syndrome in patients with Tension-Headache and its correlation with clinical outcome.Material and method:1.Data Mining:Literature related to TCM treatment of Blood-Stasis headache in VIP database,CNKI database,Wanfang database and Pub Med were searched,and databases were established using Excel 2013,SPSS Modeler 18.0 and SPSS 25.0.Frequency analysis,association rule analysis and cluster analysis are carried out respectively.2.Randomized controlled trial study:74 patients with Tension-Type Headache(syndrome of Qi-Stagnation and Blood-Stasis)in the outpatient department and ward of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine were enrolled from December 2018-December 2021 and were assigned to Xuefu Zhuyu oral liquid group and placebo group in a ratio of 1:1.The experimental group was treated with Xuefu Zhuyu oral liquid produced by Jilin Aodong Yanbian Pharmaceutical Co.,LTD.,2 doses once,3 times a day,treatment course for 4 weeks,follow-up for 8 weeks.The control group was treated with placebo which was almost identical with Xuefu Zhuyu oral liquid in appearance,color and smell,and the usage and dosage were consistent with those of the experimental group.The main outcome index was observed:the mean difference of pain intensity before and after treatment was measured by visual analogue scale(VAS).Secondary outcome indicators were observed:headache frequency,headache duration,TCM syndrome evaluation score scale,anxiety and depression evaluation,quality of life,and hemodynamic detection.3.Observational study:Real-World clinical practice data of patients with Tension-Type Headache(Qi-Stagnation and Blood-Stasis syndrome,non-Qi-Stagnation and Blood-Stasis syndrome)were observed and collected.Patients with Tension-Type Headache who met the diagnostic criteria were collected from the outpatient department or ward of the affiliated Hospital of Liaoning University of Traditional Chinese Medicine and entered into the disease registration cohort.Clinicians registered each patient and collected the baseline data of the patients.Patients with Qi-Stagnation and Blood-Stasis syndrome in the registration cohort were screened into the Qi-Stagnation and Blood-Stasis syndrome group,and those who did not meet the conditions of Qi-Stagnation and Blood-Stasis syndrome were selected into the non-Qi-Stagnation and Blood-Stasis syndrome group.The two groups of patients were enrolled in the observational study,and the general information,clinical manifestations,syndroms,medication and other treatment records,disease changes,physical and chemical examination,adverse events and other information were collected.Results:1.Data mining results:According to the screening criteria,a total of 132 literatures were included,and 132 prescriptions of traditional Chinese medicine for the treatment of Blood-Stasis headache were collected,involving 152 flavors of Traditional Chinese Medicine.The top 3 drug frequencies were Chuanxiong,Angelica and Safflower;The main drug efficacy categories were Blood-Activating and Blood-Stasis removing drugs;The highest frequency of channel conversion was liver channel;The highest frequency of sex and taste were warm drugs and bitter drugs;Through association analysis and cluster analysis,20 drug association rules and 5 new clusters were obtained,among which the core drug pair combination was"Chuanxiong-Angelica".2.Results of Randomized Controlled Trials:(1)Main outcome indicators:mean difference in pain intensity before and after treatment,measured by visual analogue scale(VAS).By independent sample t test,there was no statistically significant difference in the average pain intensity VAS between the two groups before treatment(P>0.05),but there was statistically significant difference in the average pain intensity VAS between the two groups at the 4th and8th week after treatment(P<0.05),and the experimental group was better than the control group(P<0.05).At the 12th week after treatment,there was no statistically significant difference in the average pain intensity VAS between the two groups(P>0.05).Repeated measurement ANOVA was performed on the VAS of the experimental group and the control group before treatment,at 4,8 and 12 weeks after treatment,and the average pain intensity VAS was significantly different before treatment,at 4,8 and 12 weeks after treatment(P<0.05).(2)Secondary outcome indicators:(1)Comparison of the number,days and duration of headache attacks in each observation period:Repeated measurement analysis of variance was performed on the number,days and pain time of headache attacks in the experimental group and the control group before treatment,4 weeks,8 weeks and 12 weeks after treatment.The three differences were statistically significant before treatment,4 weeks,8 weeks and 12weeks after treatment(P<0.05),and there was no statistically significant difference in the interaction effect between different groups.(2)Analysis of effective rate:The average effective rate of headache intensity in the 4th week was 50.34%(95%CI=38.46%～62.22%)in the experimental group and 33.13%(95%CI=23.62%～42.64%)in the control group.After t test,t=2.294,P=0.025,the average effective rate of headache intensity was 50.34%(95%CI=38.46%～62.22%).The difference was statistically significant(P<0.05).The average effective rate of headache intensity in the 8th week was 57.57%(95%CI=45.95%-69.20%)in the test group and 41.34%(95%CI=31.21%-51.47%)in the control group.After t test,t=2.134,P=0.036,the average effective rate was 57.57%(95%CI=45.95%-69.20%).The difference was statistically significant(P<0.05).(3)Comparison of Zung-SAS and Zung-SDS before and after treatment:Repeated measurement analysis of variance was performed on the Zung-SAS and Zung-SDS of the experimental group and the control group before treatment,4weeks,8 weeks and 12 weeks after treatment.The differences of these two items were statistically significant before treatment,4 weeks,8 weeks and 12 weeks after treatment(P<0.05),and there was no statistically significant difference in the interaction effect between different groups.(4)Comparison of the total scores of TCM syndroms before and after treatment:Repeated measurement analysis of variance was performed on the total scores of TCM syndromes of the experimental group and the control group before treatment,4 weeks,8weeks and 12 weeks after treatment.The differences of these two items were statistically significant before treatment,4 weeks,8 weeks and 12 weeks after treatment(P<0.05),and there was no statistically significant difference in the interaction effect between different groups.The average effective rate of the experimental group was 56.81%(95%CI=44.36%～69.25%),and the average effective rate of the control group was 40.03%(95%CI=28.46%～51.61%).After t test,t=2.005,P=0.049.The difference was statistically significant(P<0.05).(5)Hemodynamic detection:Transcranial Doppler ultrasonography(TCD)was used,and the detection indicators included the systolic peak velocity(VS),the end-diastolic peak velocity(VD),the average blood flow velocity(VM)and the pulsation index(PI)of the middle cerebral artery(MCA),the anterior cerebral artery(ACA),the posterior cerebral artery(PCA),the vertebral artery(VA)and the basilar artery(BA).Among them,only the left vertebral artery pulse index PI before and after treatment had statistical significance between the groups(P<0.05),and the rest were not statistically significant.(6)Health questionnaire(EQ-5D-5L):In terms of mobility,self-care and daily activities,independent sample t test showed no statistical significance in daily activities scores between the two groups before treatment,at the 4th week and 12th week after treatment(P>0.05).Repeated measurement ANOVA was performed on the daily activity scores of the test group and the control group before treatment,4 weeks after treatment and 12 weeks after treatment,and the statistical analysis results showed that there was no statistical significance in the differences of each item before treatment,4 weeks after treatment and 12 weeks after treatment(P>0.05).In terms of pain,anxiety or depression,and health status,there were no statistically significant differences in daily activity scores between the two groups before treatment,4 weeks after treatment and 12 weeks after treatment by independent sample t test(P>0.05).Repeated measurement ANOVA was performed on the daily activity scores of the experimental group and the control group before treatment,4 weeks and 12 weeks after treatment,and the statistical analysis results showed that there were statistically significant differences in each item before treatment,4 weeks and 12 weeks after treatment(P<0.05).(7)University of Pittsburgh Sleep Quality Questionnaire:Through repeated measure ANOVA,the hours spent falling asleep each night were significantly different before treatment,at 4 weeks and 12 weeks after treatment(P<0.05),and the trend of experimental group was more obvious than that of control group;The data of not falling asleep within 30min were tested by Fisher exact probability method before treatment and at the 12th week after treatment,χ2=11.905,P=0.002,the difference was statistically significant(P<0.05).There was no significant difference in the interaction effect between different groups,indicating that the improvement of symptoms was independent of time.According to repeated measurement ANOVA,there were significant differences in sleep hours per night before treatment,4 weeks and 12 weeks after treatment(P<0.05),and the trend of experimental group was more obvious than that of control group.There was no statistically significant difference in the interaction effect between different groups,indicating that the improvement of symptoms was independent of time;In terms of improving sleep disorders,Xuefu Zhuyu oral liquid could improve the participant’s breathing and keep them enthusiastic about completing certain tasks,and the effect was better than placebo at the 12th week.Safety evaluation:During the whole treatment process,no obvious adverse drug reactions occurred in the two groups of patients,and no obvious abnormalities were found in the four tests of blood routine,urine routine,liver function,kidney function and coagulation in the experimental group after treatment,suggesting that the clinical application of this drug is safe and reliable.3.Observational results:(1)In terms of occupation,there were 10 workers(13.50%),17professional and technical personnel(23.00%),29 retirees(39.20%),and 18 others(24.30%)in the Qi-Stagnation and Blood-Stasis group.In the non-Qi-Stagnation and Blood-Stasis group,there were 9 workers(6.50%),14 professional and technical workers(10.10%),62 retired workers(44.90%),and 53 other workers(38.40%).Chi-square test,χ=11.270,P=0.010,the difference was statistically significant(P<0.05).(2)In terms of the frequency of headache attacks,the minimum frequency of headache attacks in Qi-Stagnation and Blood-Stasis group was 2 times,and the maximum was 90times,with an average of(13.15±15.45)minutes;The number of headache attacks in the non-Qi-Stagnation and Blood-Stasis group was the minimum2 times and the maximum 58 times,and the average score was(9.61±9.82)minutes.After t test,t=2.034,P=0.043,the difference was statistically significant(P<0.05).(3)In terms of the days of headache attack,the minimum days of headache attack in Qi-Stagnation and Blood-Stasis group were 2 days and the maximum was 30 days,with an average of(8.74±5.52)days;The days of headache attack in the non-Qi-Stagnation and Blood-Stasis group were the minimum 2days and the maximum 23 days,and the average score was(6.51±4.76)days.After t test,t=3.071,P=0.002,the difference was statistically significant(P<0.05).(4)For anxiety and depression,the minimum score of Zung-SDS in Qi-Stagnation and Blood-Stasis group was 25,the maximum score was 61,and the average score was 38.08±10.60.In the non-Qi-Stagnation and Blood-Stasis group,the minimum Zung-SDS score was 25,the maximum score was 63,and the average score was 34.35±8.28.The difference between the two groups was not uniform.After t’test,t=2.630,P=0.010,the difference was statistically significant(P<0.05).(5)In terms of physical and chemical examination,the minimum WBC count in Qi-Stasis and Blood-Stasis group was 3.53×10~9/L,and the maximum was 10.36×10/L,with an average of(6.61±1.60)10/L;The minimum WBC count in the non-Qi-Stagnation and Blood-Stasis group was 2.52×10~9/L,and the maximum was 11.37×10/L,with an average of(6.00±1.54)10/L.After t test,t=2.715,P=0.007,the difference was statistically significant(P<0.05).(6)In terms of hemodynamic indexes:the average blood flow velocity and right pulsation index of middle cerebral artery Qi-Stagnation and Blood-Stasis group were significantly different from those of non-Qi-Stagnation and Blood-Stasis group(P<0.05);The bilateral average blood flow velocity of the anterior cerebral artery Qi-Stagnation and Blood-Stasis group was significantly different from the non-Qi-Stagnation and Blood Stasis group(P<0.05);The left average blood flow velocity and left pulse index in the posterior cerebral artery Qi-Blood Stasis group were significantly different from those in the non-Qi-Blood-Stasis group(P<0.05).The right vertebral artery pulsation index was statistically significant compared with the non-Qi-Stagnation and Blood-Stasis group(P<0.05).Conclusion:1.Data mining research suggests that Xuefu Zhuyu decoction can be used as the first choice basic prescription for treating blood stasis headache.2.Randomized Controlled Trial study confirmed:Xuefu Zhuyu oral liquid in the treatment of tension headache syndrome of Qi-Stagnation and Blood-Stasis and its accompanying symptoms,the clinical effect is accurate,no obvious adverse reactions,and can effectively reduce the TCM syndrome score of patients,worthy of further clinical promotion.3.Observational studies have shown that patients with tension headache syndrome of Qi-Stagnation and Blood-Stasis have more headache attacks,longer attack days,and are more prone to depression than those without Qi-Stagnation and Blood-Stasis syndrome.The difference in hemodynamics is significant. |
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