From clinical appearance to accurate management in acute ischemic stroke patients: With the guidance of innovative traditional Chinese medicine diagnosis

Abstract Objective To investigate the correlation between simplified classification and laboratory indicators in patients with acute ischemic stroke, also provide accurate evidences for simplified classification and guide clinical interventions and treatment. Methods Two hundred patients with acute ischemic stroke were classified into four types according to the characteristics of Traditional Chinese Medicine syndrome: phlegm‐heat syndrome, phlegm‐dampness syndrome, qi deficiency syndrome, and yin deficiency syndrome. The differences between the types of syndromes and the correlation between laboratory indicators and syndromes were analyzed. Results Among the 200 patients with acute ischemic stroke, there were significant differences in the level of low‐density lipoprotein (LDL‐C) (p < .05) between patients with phlegm‐heat syndrome and other three types. There were significant differences in the levels of homocysteine (HCY) and fibrinogen (Fib) between patients with yin deficiency syndrome and other three types (p < .05). In addition, there were statistically significant differences in blood glucose (Glu), glycosylated hemoglobin (HBA1c), and total cholesterol (CHO) between phlegm‐heat syndrome and qi deficiency syndrome (p < .05). There were significant differences in the levels of Glu, HBA1c, D‐2 polymer (D‐D), and C‐reactive protein (CRP)s between patients with phlegm‐heat syndrome and phlegm‐dampness syndrome (p < .05). There were statistically significant differences in the levels of CRP and urea nitrogen between patients with yin deficiency syndrome and phlegm‐dampness syndrome and qi deficiency syndrome (p < .05). Conclusions The four‐type simplified classification of Integrated TCM and Western medicine in acute ischemic stroke has specific laboratory data to support. Simplified classification with TCM treatment and intervention of different patients improves the survival and treatment, which is an innovative, easy‐to‐master clinical diagnosis and treatment model.


| INTRODUC TI ON
Acute ischemic stroke is one of the major disabling and lethal diseases in the world that has become the first cause of death in China with its increasing incidence and younger trend (Chen, 2008). At present, Western medicine treatment is mainly based on basis such as thrombolysis, anti-platelet aggregation, lipid-lowering, spots stabilization, blood pressure control, and blood glucose control, which lacks individualized treatment plans and new treatment ideas. The disease belongs to the category of "stroke disease" in traditional Chinese medicine, with standardization of syndromes and clinical application are attracting more and more attention (Zhao, Zhang, & Li, 2018). Therefore, simplifying syndrome differentiation is especially important for clinical diagnosis and treatment. An in-depth study of TCM syndromes and integrated into Western diagnostics has been proposed, leading to a new medical model diagnosis and treatment program (Jiang et al., 2012).

| Traditional Chinese medicine acute ischemic stroke syndrome (Xuanwu classification)
The classification of phlegm-heat syndrome, phlegm-dampness syndrome, qi deficiency syndrome, and yin deficiency syndrome was depending on the TCM characteristics of syndromes (Table 1).

| Exclusion criteria
(a) Suffering from serious systemic diseases that may affect the outcome, such as liver and kidney disease, blood system diseases, autoimmune diseases, malignant tumors, chronic serious infections, mental illness, drug abuse, alcoholics, and so on. (b) Poor fit and poor compliance.

| Research methods
In all cases, blood and urine samples were collected with an empty stomach condition on the next morning of the hospitalization, and laboratory indicators were collected. Biochemical series: blood  According to the characteristics of syndromes, the symptoms of each patient were objectively recorded and simplified. The specific descriptions included facial color, tongue image, onychomycosis, high and low sound, bad breath, defecation, sweating, the preference of drinking and diet, and the temperature of hands and feet.
The significant differences between the various laboratory indicators in the four types of syndromes were analyzed.

| Statistical methods
The data were sorted by Microsoft Excel 2010 and processed and analyzed by SPSS 17.0. The continuous variables were expressed by ± s, and the t test was used for comparison. The classified variables were expressed as percentage, and the chi-square test was used for comparison. p < .05 was considered statistically significant.

| D ISCUSS I ON
The four-type simplified classification syndrome characteristics of TCM in acute ischemic stroke were as described above. In the classification of syndrome type, tongue diagnosis plays an important role (Liu et al., 2014), and the characteristics of tongue images are as follows.
Modern research shows that cerebral arteriosclerosis is the pathological basis of cerebrovascular disease, while lipid metabolism disorder, hypercoagulable state, and vascular inflammatory injury are keys to the occurrence of cerebral arteriosclerosis (Ding, 2010).
The above analysis is on the syndrome characteristics of the four types. Exploring the specific laboratory indicators which related to the four types to provide an objective laboratory basis for the syndrome classification helps to objectively judge the syndrome type and to correlate the pathological basis, enriching the theoretical content of Integrative Chinese and Western Medicine.
In this study, it is found that the proportion of patients with phlegm-heat syndrome was the highest (65%), whose level of LDL-L was higher than that of other type 3 with statistically significance  levels (Shi, Wang, & Wang, 2013). There are traditional Chinese medicine studies on lipid-lowering mainly using methods such as Shengqing Jiangzhuo with Chinese herbal medicines such as red yeast, rhubarb, hawthorn and Polygonum multiflorum (Pang, Zhao, & He, 2016). There are statistically significant differences in Glu and HBA1c levels between patients with phlegm-heat syndrome and phlegm-dampness syndrome and qi deficiency syndrome, and in D-D and CRP levels between patients with phlegm-heat syndrome and phlegm-dampness syndrome. Some studies have found that patients undergoing whole cerebral angiography (DSA) experience varying degrees of inflammatory response, manifested as elevated levels of CRP, Fib, and so on, with clinical manifestations of phlegmheat syndrome. The intervention group was treated with Tanhuo prescription on the basis of conventional treatment in the control group, whose serum CRP and Fib were significantly decreased, while the indexes of the control group were increased, which indicated that the prescription has certain anti-inflammatory, anti-platelet, and fibrin-lowering effects. It has been confirmed by basic researches (Gao, Wang, & Liu, 2008;Liu, Luo, & Gao, 2009;Xu, Gao, & Song, 2010 Chinese herbal medicine Coptis has a certain hypoglycemic effect (Gu, Wang, & Pang, 2017), which after the prescription still requires further studies. After clinical syndrome classification, more attention should be paid to the inflammatory index, blood glucose, glycosylated hemoglobin, and low-density lipoprotein level, and more strict management of its hypoglycemic and lipid-lowering drugs should be carried out.
According to the traditional Chinese medical concept, the correlation between qi deficiency and phlegm-dampness is high, and qi deficiency ends up in phlegm-dampness. Ji Wang found that patients with phlegm-dampness syndrome have four up-regulated genes and six down-regulated genes, who are more susceptible to diseases such as hypertension and diabetes that increase the risk of stroke TA B L E 7 Comparison of the laboratory indicators between the four syndrome types . Studies have shown that gastrointestinal dysfunction leads to folic acid and vitamin absorption disorders induced high HCY, which in turn leads to atherosclerotic diseases including cerebrovascular disease. Other studies have shown that folic acid and vitamin B family do not directly improve cognitive impairment in the elderly, but reduce the incidence of cardiovascular and cerebrovascular diseases by reducing HCY levels (Sacco et al., 2006). In this study, there was no correlation between folic acid, vitamin B12 content and HCY content. Although there was no statistically significant difference in folic acid between patients with qi deficiency syndrome and other three types, the average level of folic acid in patients with qi deficiency was significantly lower than that of the other three syndromes, which provides some reference value for the clinic. Modern research believes that oral administration of folic acid and vitamin B12 drugs reduces the level of HCY to reduce the incidence of cerebrovascular disease, which has preventive significance (Liu et al., 2014). A previous study randomly divided 206 patients into observation group and control group with patients in the observation group given folic acid tablets (5 mg qd) orally, whose HCY levels were significantly decreased. After 12 months of follow-up, the incidence of stroke and myocardial infarction in the control group were 12.62% and 2.91%, respectively, which were significantly higher than 1.94% and 0.97% of the observation group ( Among the 200 patients, only five had yin deficiency syndrome, whose proportion (2.5%) was the least. In order to promote the concept and method of simplifying classification, Professor Li Gao has divided the syndrome of "Yin and Yang as the general outline" according to the eight-character syndrome of Chinese medicine, and combined with years of clinical experience to divide the ischemic stroke into two types: heat syndrome and non-heat syndrome, and found two major types of patients. There is indeed an essential difference in the expression of microRNAs (miRNAs; Huang & Han, 2013), and syndromes of phlegm-heat and yin deficiency can be classified as heat syndrome. In the study, the levels of HCY and Fib in patients with yin deficiency syndrome were significantly higher than those in other types, and there were statistical differences in HCY and Fib levels. Patients with yin deficiency syndrome and phlegm-dampness syndrome and qi deficiency syndrome also had statistically significant differences in CRP and BUN levels, and their CRP and BUN levels were higher than those of other types. Although the number of cases studied was small, the CRP values of the five patients were higher than the normal level, and the D-D and Fib levels were also higher than the normal level. In comparison, it was found that the phlegm-heat syndrome and yin deficiency syndrome were higher than the phlegm-dampness syndrome and qi deficiency syndrome in the CRP and D-D levels, which coincided with the above conclusions. Although the number of cases is small, clinical attention should be paid to the inflammatory indicators of patients with yin deficiency syndrome. Studies have shown that the use of phlegm-reducing Chinese medicine improves the clinical symptoms and reduces the degree of neurological damage by reducing CRP levels (Zhang, 2018).
The conclusion of this study is that partial specific laboratory indicators of cerebrovascular disease syndrome can be used as an important reference for simplified classification. Attention should be paid to the inflammatory index, blood sugar, blood lipid level of patients with heat syndrome, to the folic acid level of patients with qi deficiency syndrome, and to the inflammatory index of patients with yin deficiency syndrome. This study also had limitations.
As this was a single center, and small scale study, this might cause higher selection biases, and we cannot establish a stable model through performing multivariate logical regression. Therefore, in the future, larger scale further studies are still needed to clarify these problems.
Under the premise of clear diagnosis of acute ischemic stroke in modern medicine, the study draws on the theory of TCM syndrome differentiation and combines the clinical experience accumulated by the Department of neurology, Xuanwu Hospital for many years to classify acute cerebrovascular disease into four types and explore possible laboratory markers. In theory, it will be objective and feasible to guide the individualized diagnosis and treatment of cerebrovascular diseases with the concepts of traditional Chinese medicine and the theory of syndrome differentiation.

CO N FLI C T O F I NTE R E S T
None declared.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.