| Study 1 The Correlation research between Calcium homeostasis regulation and Cognitive function?Syndrome elements of TCM in PSCI patientsObjective Post-stroke cognitive impairment(PSCI)is one of the most common complications after stroke,which includes cognitive impairment of different degrees,such as post-stroke cognitive impairment no dementia(PSCIND)and Poststroke dementia(PSD).How to further explore the mechanism of PSCI and how to prevent and treat PSCI early and effectively is an important medical problem that we urgently need to solve.This project based on the regulation mechanism of calcium homeostasis,by studying the correlation between calcium homeostasis regulators and the score of cognitive dysfunction in PSCI patients,the distribution of TCM syndrome elements in PSCI patients,and the relationship with the severity of cognitive dysfunction after stroke,correlation between TCM syndrome elements and calcium homeostasis regulators in PSCI patients,to explore the correlation between PSCI and calcium homeostasis regulation,and the correlation between pathogenesis “Kidney failing to nourish liver,liver wind agitation,intermin-gled phlegm and blood stasis”of PSCI and calcium homeostasis regulation.Methods ALL patients included in the encephalopathy clinic of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine and the inpatient and outpatient departments of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from January 2019 to July 2020.110 patients with PSCI were included in the PSCI group.Among them,80 patients were subdivided into PSCIND group and 30 patients into PSD group according to the degree of cognitive impairment.And 30 patients without cognitive impairment after ischemic stroke were recruited as the control group.1.Compare the medical history data between the observation group and the control group,including age,gender,education level,drinking history,smoking history,whether they have coronary heart disease,diabetes,hypertension,or hyperlipidemia,and compare cervical vascular plaques Mass condition,bone density and calcium homeostasis regulator(PTH,1,25-hydroxyvitamin D,blood calcium level)and the National Institute of Health Stroke Scale(National Institute of Health Stroke Scale,NIHSS)score.2.Analysis of the correlation between calcium homeostasis regulator PTH,1,25-hydroxyvitamin D and blood calcium levels of PSCI patients and the scores of Montreal Cognitive Assessment(Mo CA)and the mini-Mental State Examination(MMSE),which are internationally recognized and commonly used to reflect cognitive function.Multiple linear regression was used to analyze the factors affecting MMSE and Mo CA scores.3.According to the TCM Syndrome Elements Scale,the observation group patients were scored with 11 syndrome elements including kidney deficiency,spleen deficiency,qi deficiency,blood deficiency,yin deficiency,yang deficiency,pulp loss,yang hyperactivity,internal heat,phlegm turbidity,and blood stasis.Statistics the distribution of TCM syndrome elements.4.Analyze the correlation between the TCM syndrome elements of PSCI,PSCIND,PSD patients and the MMSE and Mo CA scores respectively;multiple linear regression analysis was used to analyze the relevant TCM syndrome factors that affect the MMSE and Mo CA scores in the PSCI group.5.Analyze the correlation between TCM syndrome elements and calcium homeostasis regulators in PSCI patients.Results 1.Comparing the medical history data between the PSCI observation group and the control group,the 1,25-hydroxyvitamin D and blood Calcium levels of the PSCI group were lower than those of the control group,and the difference was statistically significant(P<0.05).2.The results of Spearman correlation analysis indicated that the calcium homeostasis regulator PTH in the PSCI group was negatively correlated with MMSE and Mo CA scores(rs=-0.494,P<0.001;rs=-0.572,P<0.001);1, 25-hydroxyvitamin D was positively correlated with MMSE score(r=0.586,P <0.001);1,25-hydroxyvitamin D,blood Calcium and Mo CA score have a positive correlation(rs=0.496,P <0.01;rs=0.204,P =0.032<0.05).3.The results of multiple linear regression analysis indicated that MMSE score increased with the increase of 1,25-hydroxyvitamin D level(B=0.111,P =0.017).With the increase of NIHSS score and PTH level,Mo CA score was lower(B=-0.57,P < 0.001;B=-0.052,P < 0.001);With the increase of education level,Mo CA score was higher(B=0.853,P=0.029).4.In the PSCI group,the top frequency ranking of TCM syndrome elements are phlegm turbid(61 times,55.45%),blood stasis(56 times,50.9%),Yang hyperactivity(43 times,39.09%),and kidney deficiency(35 times,45%).The top ones in the frequency ranking of the PSCIND group were phlegm turbidity(49 times,61.25%),blood stasis(43 times,53.75%),and yang hyperactivity(31 times,38.75%);the top ones in the frequency ranking of the PSD group were kidney deficiency(17 times,56.66%),yin deficiency(13 times,43.33%),blood stasis(13 times,43.33%).The higher syndrome scores in the PSCIND group were phlegm turbidity,Yang hyperactivity,and blood stasis;the higher scores in the PSD group were kidney deficiency,yin deficiency,pulp loss,and blood stasis.5.The results of Spearman correlation analysis indicated that the PSCI group TCM syndrome elements phlegm turbidity,pulp loss,yang hyperactivity,blood stasis were negatively correlated with the MMSE score(rs =-0.268,P =0.005;rs =-0.235,P=0.013;rs =-0.206,P =0.031;rs =-0.330,P<0.001);while phlegm turbidity,kidney deficiency,pulp loss,blood stasis and Mo CA score are all negatively correlated(rs=-0.202,P=0.034;rs =-0.232,P =0.015;rs=-0.237,P =0.012;rs=-0.334,P<0.001);among them,blood stasis has the most significant correlation with MMSE and Mo CA scores.The results of multiple linear regression analysis indicate that there is a linear correlation between the pulp loss and blood stasis and the scores of MMSE and Mo CA.As the pulp loss and blood stasis scores are higher,the MMSE and Mo CA scores are lower(B=-0.319,P<0.001;B=-0.100,P=0.017;B=-0.268,P<0.001;B=-0.094,P =0.010).6.The Spearman correlation analysis of subgroups indicated that phlegm turbidity,Yang hyperactivity,and blood stasis were negatively correlated with MMSE and Mo CA scores in the PSCIND group(rs=-0.639,P<0.001;rs =-0.526, P<0.001;rs=-0.445,P<0.001;rs=-0.499,P<0.001;rs=-0.458,P<0.001;rs =-0.404,P<0.001);phlegm turbidity,kidney deficiency,pulp loss,blood stasis were negatively correlated with MMSE score in PSD group(rs=-0.550,P =0.002;rs=-0.416,P =0.022;rs=-0.385,P =0.036;rs=-0.510,P =0.004;),phlegm turbidity,kidney deficiency,blood stasis were negatively correlated with Mo CA score in PSD group(rs=-0.634,P <0.001;rs=-0.610,P <0.001;rs=-0.794,p <0.001).7.The Correlation analysis between TCM syndrome scores and calcium homeostasis regulators in the PSCI group.The results suggest that phlegm turbidity,yang hyperactivity,and blood stasis were positively correlated with PTH levels(rs=0.545,P <0.001;rs= 0.371,P <0.001;rs= 0.614,P <0.001),negatively correlated with 1,25-hydroxyvitamin D levels(rs= 0.844,P <0.001;rs=-0.605,P <0.001;rs=-0.737,P <0.001).However,kidney deficiency,pulp loss,blood stasis were negatively correlated with blood Calcium levels(rs =-0.233,P=0.003;rs=-0.226,P =0.018;rs=-0.293,P=0.002).Conclusion 1.There is a significant correlation between post-ischemic stroke cognitive impairment and regulation of calcium homeostasis.As PTH levels increased,cognitive function levels decreased;as 1,25-hydroxyvitamin D levels decreased,cognitive function decreased.The decrease of 1,25-hydroxyvitamin D level and the increase of PTH level may be the potential factors of post-ischemic stroke cognitive impairment.And there isn't a certain correlation between blood calcium and post-stroke cognitive impairment.2.Phlegm turbidity,yang hyperactivity,Kidney deficiency and blood stasis are the main syndrome elements of PSCI patients.Phlegm turbidity,yang hyperactivity and blood stasis are the main syndrome elements of PSCIND patients.Kidney deficiency,yin deficiency,pulp loss and blood stasis are the main syndrome elements of PSD patients,which may reflect the severity of cognitive dysfunction after ischemic stroke,and blood stasis may be the core risk factor of post-ischemic stroke cognitive impairment.3.Phlegm turbidness,yang hyperactivity and blood stasis scores were positively correlated with PTH and negatively correlated with 1,25-hydroxyvitamin D level,while kidney deficiency,pulp loss and blood stasis scores were negatively correlated with blood calcium level.There is a significant correlation between pathogenesis “Kidney failing to nourish liver,liver wind agitation,intermin-gled phlegm and blood stasis”of PSCI and calcium homeostasis regulation.Study 2 The Clinical Study on Calcium homeostasis regulation and Cognitive function in PSCIND patients by the Intervention of Yinaohumai prescriptionObjective In this study,the changes of cognitive function,nerve function,daily life ability,electroencephalogram and calcium homeostasis in patients with ischemic PSCIND before and after treatment were used to explore the clinical efficacy and possible mechanism of Yinaohumai prescription in treating ischemic PSCIND patients.Methods From April 2019 to May 2020,62 patients were included with TCM syndromes of liver yang hyperactivity,phlegm turbidity obstruction and blood stasis obstruction,syndrome in inpatient and outpatient of neurology department of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,and accord with the PSCIND diagnostic and inclusion criteria.According to the random number table method,the patients were divided into test group and control group randomly.Control group: Donepezil tablet,take orally,5mg once a day,changed to 10 mg once a day after 4 weeks.Test group: Yinaohumai prescription,Ligusticum wallichii 15g(equivalent to granules of 3.13g),Gastrodia granule 12g(equivalent to granules of 2.4g),Acorus tatarinowii granule 12g(equivalent to granules of 1g),Fructus alpiniae oxyphyllae granule 10g(equivalent to granules of 0.6g),1 bag each time,3 times a day,drunk with warm water.Treatment course is 12 weeks.The scores of TCM syndromes element,NIHSS scores,activities of Daily Living Scale(ADL)scores,MMSE and Mo CA scores were assessed before and after treatment on the first day of treatment and 3 months after treatment;Hematological indicators such as PTH,1,25-hydroxyvitamin D,blood calcium level and liver and kidney function.By comparing the changes of the above indicators between the two groups before and after treatment,as well as the changes of themselves before and after treatment,the clinical effect and possible mechanism of Yinaohumai prescription on patients with ischemic PSCIND were discussed.Results 1.Before treatment,there was no significant difference in NIHSS scores between the two groups(P>0.05).The scores were comparable between the two groups before treatment;After treatment the scores were lower than that before treatment,with statistical differences.But there was no significant difference in the scores between the two groups after treatment(P>0.05).2.There was no significant difference in ADL scores between the two groups before treatment(P>0.05).The scores before treatment were comparable between the two groups;after treatment,the scores of the two groups were lower than those before treatment,with significant statistical differences(P <0.001).There was no significant difference in the scores between the two groups after treatment(P>0.05).3.There was no significant difference in MMSE scores between the two groups before treatment(P>0.05),which was comparable;the MMSE scores after treatment were higher than those before treatment,with significant statistical differences(P <0.001).There was no significant difference in MMSE scores between the two groups after treatment(P>0.05).4.There was no statistically significant difference in Mo CA scores between the two groups before treatment(P>0.05).The Mo CA scores of the two groups after treatment were higher than those before treatment,with significant statistical differences(P <0.001).There was no statistically significant difference in Mo CA scores between the two groups after treatment(P <0.05).5.Before treatment,the two groups of patients had no statistically significant difference in executive ability,visuospatial ability,attention,language,memory and other cognitive domain scores(P >0.05).After treatment,the scores of executive ability,visuospatial ability,attention and memory in the two groups were significantly higher than those before treatment,and the differences were statistically significant(P<0.05).In terms of language ability,the language score of the control group after treatment was not statistically different from that before treatment(P >0.05);the language score of the test group after treatment was higher than that before treatment,and the difference was statistically significant(P <0.05). 6.There was no significant difference in EEG abnormalities between the two groups before treatment(P>0.05).After treatment,the two groups were improved significantly compared with before treatment,and the difference was statistically significant(P <0.05).After treatment,there was no significant difference in EEG abnormalities between the two groups(P >0.05).7.There was no statistically significant difference in the levels of PTH,1,25-hydroxyvitamin D,and blood calcium between the two groups before treatment(P>0.05).After treatment,the PTH levels of the two groups decreased compared with before treatment,and the difference was statistically significant(P <0.05);after treatment,the levels of 1,25-hydroxyvitamin D and blood calcium were higher in the two groups than before treatment,and the difference was statistically different(P <0.05).There was no significant difference in the levels of PTH,1,25-hydroxyvitamin D and blood calcium between the two groups after treatment(P <0.05).8.In terms of the improvement of TCM syndromes,the total effective rate of the test group was 93.75% after treatment;the total effective rate of the control group was 73.33%,the difference was statistically significant(P <0.05).Conclusion 1.Yinao Humai prescription can significantly improve the daily life ability,neurological function and EEG of ischemic PSCIND patients.It can significantly improve the cognitive function of these patients,and its clinical efficacy is comparable to donepezil in improving executive ability,visuospatial ability,attention,memory ability.But Yinao Humai prescription was significantly better than donepezil in improving language ability.2.In terms of the improvement of TCM syndromes,for the patients with liver yang hyperactivity,phlegm turbidity obstruction and blood stasis obstruction,the effect of Yinaohumai prescription in improving TCM syndromes was obviously better than that of donepezil group significantly.3.After treatment in test group,PTH level decreased,1,25-hydroxyvitamin D,blood calcium increased,which were statistically significant.It indicating that Yinao Humai prescription may protect brain tissue and improve cognitive function by regulating calcium homeostasis in patients with ischemic PSCIND. |
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