Coronary heart disease （CHD） has a distinct circadian rhythmicity in its onset， which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind"， this paper explores the pathogenic evolution rules of qi-blood disharmony， channel obstruction， interacting as cause and effect with circadian rhythm disorders in CHD. Clinically， CHD can be observed to attack in the early morning， at night， in the afternoon， and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation， yin deficiency with yang floating， qi and yin deficiency， and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time， regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages， and select the appropriate timing for administration to harness natural timing. At the Mao （卯） hour， yang ascends while yin descends， and taking medication at this time conforms to the ascending of yang qi. At the Wu （午） hour， the heart meridian is active， and taking medication at this time warms the channel passages and assists heart yang， which can be treated with modified Buzhong Yiqi Decoction （补中益气汤） or Shengyang Yiwei Decoction （升阳益胃汤）. At night， blood should be harmonized， when the channel passages are unblocked through nourishing， restraining， and searching， with Lianmei Decoction （连梅汤） combined with Dahuang Zhechong Pill （大黄䗪虫丸）. Following the temporal rhythm， the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises， resonating and corresponding with the natural rhythm.

Myocardial ischemia-reperfusion injury （MIRI） is a common injury in the treatment of ischemic heart diseases. MIRI can be categorized as chest impediment and palpitation in traditional Chinese medicine， with the pathogenesis related to Qi and blood disharmony. The simultaneous disorders of Qi and blood are the key mechanism of MIRI， and thus the differentiation of Qi and blood syndromes is the prerequisite for the treatment. The theory of Qi and blood interacting in vessels is proposed by our team based on Qi being the commander of blood and blood being the mother of Qi as well as previous pharmacological studies. Specifically， Qi marshals blood by vessels， and the blood carries Qi by vessels. Accordingly， Qi and blood interact in the vessels. MIRI is accompanied by mitochondrial dysfunction， platelet function abnormality， and vascular endothelial damage， which are correlated with Qi deficiency， blood stasis， and vessel damage， respectively. Mitochondrial， platelet， and vascular endothelial structural and functional changes triggered by their interactions are one of the mechanisms by which Qi deficiency， blood stasis， and vessel damage lead to the occurrence and development of MIRI. By exploring the correlations between Qi and mitochondria， between blood and platelets， and between vessels and blood vessels， we can explain the modern scientific content of the theory of Qi and blood interacting in vessels in traditional Chinese medicine. According to the pathogenesis of Qi and blood disharmony in vessels， we discussed the pharmacological mechanisms of Qi-replenishing medicines， blood-activating medicines， and their combinations in the prevention and treatment of MIRI. On the basis of the research achievements in the prevention and treatment of MIRI by Qi-replenishing and blood-activating Chinese medicines based on the theory of Qi and blood interacting in vessels， we analyzed the effects of these medicines on Qi， blood， and vessels. According to the theory of Qi and blood， this article reveals the theoretical basis and scientific connotations of the prevention and treatment of cardiovascular diseases， with the aim of providing new ideas and references for the clinical application of traditional Chinese medicine in the prevention and treatment of cardiovascular diseases.

OBJECTIVETo assess the association of CYP2C19 gene polymorphisms with the incidence of ischemic stroke among patients receiving clopidogrel therapy following coronary stenting for coronary artery disease.

METHODSClinical data of patients receiving clopidogrel therapy after coronary stenting were retrospectively studied. For a case-control study, 137 patients with acute cerebral infarction and 122 non-stroke patients were selected. Based on the variants of the CYP2C19 gene detected by a DNA microarray assay, the patients were further divided into the wild-type group(CYP2C19*1/*1) and mutant group(defined by the presence of at least one loss-of-function allele, including CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The incidences of ischemic stroke in the two groups were compared through a chi-square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel therapy on the incidence of ischemic stroke was analyzed through multivariable logistic regression.

RESULTSA total of 259 patients were enrolled. The case and control groups showed no difference in terms of gender and age. There were 123 cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant group. The incidence of ischemic stroke of mutant group was significantly higher than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried a 1.13 times greater risk for ischemic stroke compared to wild-type genotype (OR=2.13, 95%CI: 1.23-3.71).

CONCLUSIONThe efficacy of clopidogrel for the prevention of ischemic stroke in post-coronary stent patients may be reduced by the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should be adjusted based on its polymorphisms.

Brain Ischemia ; prevention & control ; Cytochrome P-450 CYP2C19 ; genetics ; Genotype ; Humans ; Percutaneous Coronary Intervention ; adverse effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymorphism, Genetic ; Stents ; adverse effects ; Stroke ; prevention & control ; Ticlopidine ; analogs & derivatives ; therapeutic use