[Editorial explanation for Expert consensus statement on Diemailing Kudiezi Injection in clinical practice].

Expert consensus statement on Diemailing Kudiezi Injection in clinical practice was approved on April 17,2019 by the Standardadization Office of the Chinese Association of Chinese Medicine. This project,which started in November 2017,has been developed and completed in accordance with the standard developing procedure. This paper will give a detailed introduction to the compilation process about the consensus. The aim is to enable readers to understand the background,purpose and basis of this consensus in a timely manner. Readers can learn about diffferent stages of develping process,including project management system,drafting,consulting,expert consensus,as well as current problems and shortcomings. Such an editorial explanation is just a dynamic follow-up of the whole consensus-making process. It also plays a good supervisory role in the whole consensus-making. It could be a guarantee for the quality of the consensus. There is no doubts that the editorial explanation is an important auxiliary document in the process of consensus-making. It is the extension and supplement of consensus content and a basis for fully understanding the technical content of this consensus. Therefore it is an indispensable document in the process of consensus-making.

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

Obstructive sleep apnea increases the risk of cardiac events after percutaneous coronary intervention: a meta-analysis of prospective cohort studies.

PURPOSE: Recent studies have shown an association between obstructive sleep apnea (OSA) and coronary artery disease; however, the association between OSA and cardiac outcomes in patients after percutaneous coronary intervention (PCI) remains undetermined. METHODS: PubMed, EMBASE, and CENTRAL were searched from inception to July 2016 for cohort studies that followed up with patients after PCI, and evaluated their overnight sleep patterns within 1 month for major adverse cardiac events (MACEs) as primary outcomes including cardiac death, non-fatal myocardial infarction (MI), and coronary revascularization and secondary outcomes including re-admission for heart failure and stroke. Outcomes data were pooled using fixed-effect meta-analysis, and heterogeneity was assessed with the I 2 statistics. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale checklist, and publication bias was evaluated by a visual investigation of funnel plots. RESULTS: We identified seven pertinent studies including 2465 patients from 178 related articles. OSA was associated with MACEs (odds ratio [OR], 1.52, 95% confidence interval [CI], 1.20-1.93, I 2 = 29%), which included cardiac death (OR 2.05, 95% CI, 1.15-3.65, I 2 = 0%), non-fatal MI (OR 1.59, 95% CI, 1.14-2.23, I 2 = 15%), and coronary revascularization (OR 1.69, 95% CI, 1.28-2.23, I 2 = 0%). However, OSA was not associated with re-admission for heart failure (OR 1.71, 95% CI, 0.99-2.96, I 2 = 0%) and/or stroke (OR 1.68, 95% CI, 0.91-3.11, I 2 = 0%) according to the pooled results. CONCLUSIONS: In patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal MI, and coronary revascularization.

[Dynamic Visible Microcirculation and Activating Blood Removing Stasis Research].

The technology of dynamic visualization microcirculation is to observe changes of mi- crocirculation by using visualization technology, combined with fluorescence labeling, high-speed video, electronic microscopy and other methods, converting rest images into dynamic visual graphics. In the past ten years, domestic researchers used this technology, and carried out researches on the heart, piamater/mesenteric microcirculation, dynamically observed effects of activating blood removing stasis (ABRS) research monomer, single herb and compound on arteriole/venula diameter, and the velocity of red blood cell, white blood cell adhesion, platelet aggregation, microvascular permeability, superoxide production, and plasma albumin leakage, etc. Microcirculation detection technologies were further opti- mized. Exerting direct advantages of dynamic visualization microcirculation, systematically evaluating ac- tion mechanism of Chinese herbs (multi-sites and multi-targets) , and interaction mechonism between Chinese herbs and Western drugs are important directions for future researches on microcirculation.

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization.

AIM: We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME). METHODS: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses. RESULTS: Pretreatment with the combination of ligustrazine (27 mg·kg(-1)·d(-1)) and berberine (90 mg·kg(-1)·d(-1)) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1ß, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg(-1)·d(-1)). CONCLUSION: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.

[Research on Precision Medicine, Gene Polymorphism, and Combination of Disease Identification and Syndrome Typing on Cardiovascular Diseases].

With the fusion and application of biological and information technologies in clinical practice, precision medicine has become a more precise positioning and sublimation of individualized medicine. Based on the concept of precision medicine, great developments have taken place in genetic diagnosis and targeted therapy of lung cancer, leukemia, breast cancer and other diseases, genetic diagnosis of cardiovascular diseases, and researches on gene polymorphisms and combination of disease identification and syndrome typing. However, there are still some problems. In the big data analysis era, how to organically combine precision medicine with essence research of syndromes, how to establish a new methodological system based on basic theories of Chinese medicine (CM) in accordance with clinical practice of CM and integrative medicine (IM) are both the difficulties and breakthrough points for Chinese medicine and pharmacy (CMP). They are of significance in promoting modernization of CMP.

[Chinese Herbal Compounds for Supplementing Qi and Activating Blood Circulation Combined with Dual Antiplatelet Drugs Alleviated Human Umbilical Vein Endothelial Cell Injury and Platelet Adhe- sion via Up-regulation of P13K/Akt Pathway].

OBJECTIVE: To observe the effect and underlying mechanism of Chinese herbal com- pound (CHC) for supplementing qi and activating blood circulation (SQABC) combined with dual antiplatelet drugs (DA) on oxidized low density lipoprotein (ox-LDL) induced human umbilical vein endothelial cell (HUVEC) injury and platelet adhesion evoked by injured endothelial cells (ECs) based on P13K/Akt signaling pathway. METHODS: HUVECs were randomly divided into 5 groups, i.e., the blank control group, the model group (80 mg/L ox-LDL) , the DA group (15 µg/mL aspirin +10 µg/ mL clopidogrel +80 mg/L ox-LDL) , the Panax Quinquefolium saponins ( PQS, 160 µLg/mL) + Panax Notoginseng saponins (PNS, 160 µg/mL) +DA group, the LY294002 (30 µg/mL) + PQS + PNS + DA group. HUVEC apoptosis rate and platelet adhesion to HUVECs were detected by flow cytometry. Concentration of lactate dehydrogenase ( LDH) in HUVEC supernatant was detected by biochemical assay. Concentration of intercellular adhesion molecular ([CAM) was detected by radioimmunoassay. Protein expressions of p-P13K and p-Akt in HU- VECs were detected by Western blot. RESULTS: Compared with the blank control group, the apoptosis rate of HUVECs, mean fluorescence indicator ( MFI) , concentrations of both LDH and ICAM increased (P <0. 05) , and p-Akt protein expression decreased (P <0. 05) in the model group. Compared with the model group, the apoptosis rate of HUVECs and LDH concentration increased (P <0. 05), concentrations of MFI and ICAM obviously decreased (P <0. 05) in the DA group. The apoptosis rate, MFI, concentrations of both LDH and ICAM all decreased in the PQS + PNS + DA group (P <0. 05). p-Akt protein. expres- sion in HUVECs obviously increased in the PQS + PNS + DA group (P <0. 05). Compared with the DA group, HUVEC apoptosis rate, MFI, concentrations of both LDH and ICAM in supernatant obviously decreased, p-Akt expression in HUVECs increased in the PQS + PNS + DA group (all P <0. 05). p-Akt protein expression in HUVECs was inhibited after adding specific P13K inhibitor LY294002. Protection men- tioned above all disappeared in the PQS + PNS + DA group (P <0. 05). CONCLUSION: CHC for SQABC combined with DA could alleviate ox-LDL induced apoptosis of endothelial cells and reduce injured ECs e- voked platelet adhesion via up-regulation of P13K/Akt pathway in ECs.

[Thinking on the Relationship of Formulas Corresponding to Diseases in Chinese Medicine].

"Treatment based on diseases identification and formulas corresponding to diseases" is one of important therapy modes of Chinese medicine. Although it originates from Huangdi Neijing, it is seldom systematically discussed. Modern Chinese medicine (CM) now faces diseases mostly with comparatively confirmed Western medical diagnoses. Most of them have specific pathophysiological changes. How to interpret these specific pathophysiological changes, play CM's advantages, and improve clinical efficacies has become an inevitable problem for modern CM in clinic. Authors expounded historic development and clinical application of "formulas corresponding to diseases", and its difference from "formulas corresponding to syndromes", put forward that we should combine "formulas corresponding to diseases" and "formulas corresponding to syndromes" in CM clinics. We should focus on the disease and summarize treatment rules, thereby improving targeted CM formulas.

[Effect of Chinese herbal drug-containing serum for activating blood, activating blood and dispelling toxin on TNF-alpha-induced adherence between endothelial cells and neutrophils and the expression of MAPK pathway].

OBJECTIVE: To explore the effect of drug-containing serum of Chinese herbal compounds [Xiongshao Capsule (XS, for activating blood) and Huanglian Capsule (HL, for dispelling toxin)] on tumor necrosis factor-alpha (TNF-alpha)-induced adherence between human umbilical vein endothelial cells (HUVECs) and polymorphonuclear neutrophils (PMN), inflammatory reaction and expression of related proteins in mitogen-activated protein kinase (MAPK) pathway. METHODS: Thirty-two rats were randomly divided into four groups (8 in each group) using random digit table: the blank control group treated with distilled water, the test group I treated with Chinese herbal compound of XS (0.135 g/kg), the test group II treated with Chinese herbal compound of HL (0.135 g/kg), and the test group Ill treated with Chinese herbal compound of XS (0.135 g/kg) and HL (0.135 g/kg). All medication was given by gastrogavage once a day for a week. Rats' blood serum was harvested 1 h after the last administration to prepare drug-containing serum. HUVECs were exposed to TNF-alpha (100 ng/mL) to induce cell injury model and incubated with corresponding drug-containing serum (10%) for 24 h. Normal rats' serum was given to cells in the blank control group and the model group, while XC + HL containing serum was given to cells in the rest 3 groups. The adherence of HUVECs and PMN cells was detected by using rose bengal strain. Levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and interleukin-1beta (IL-1P) in the supernatant of cultured HU-VECs were determined by ELISA. Protein expressions of mitogen-activated protein kinases p38 (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK 12) were determined by Western blot. RESULTS: Compared with the blank control group, HUVECs were seriously injured; PMN adherence amount significantly increased; levels of E-selectin, ICAM-1, and IL-1beta increased; expression levels of p-p38MAPK and p-ERK 1/2 in the supernatant of HUVECs significantly increased in the model group (all P < 0.01). Compared with the model group, HUVECs-PMN adherence amount decreased (P < 0.05); levels of E-selectin, ICAM-1, and IL-1 beta in the supernatant of HUVECs decreased (P < 0.01, P < 0.05); expression levels of p-p38MAPK and p-ERK 1/2 of endothelial cells decreased in the test group I, II, and III (P < 0.01). CONCLUSIONS: Drug-containing serums of activating blood, activating blood and dispelling toxin could attenuate TNF-alpha induced injury of HUVECs, inhibit HUVECs-PMN adherence and the release of adhesion factors. Its mechanism might be involved with protein phosphorylation of p38MAPK and ERK 1/2 in the MAPK pathway.

[Efficacy of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus after Percutaneous Coronary Intervention: a Clinical Observation].

OBJECTIVE: To observe the efficacy of Chinese herbs for supplementing qi and activating blood circulation (CHSQABC) on patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM) after successful percutaneous coronary intervention (PCI). METHODS: In this ChiCTR-TRC-00000021, a total of 281 ACS patients complicated with type 2 DM after successful PCI were randomly assigned to the Western medicine treatment group (the control group, treated by routine Western medicine treatment) and the combined treatment group (the treatment group, treated by CHSQABC + routine Western medicine treatment). Patients in the combined treatment group took Xinyue Capsule (2 pills each time, 3 times per day) and Compound Chuanxiong Capsule (2 pills each time, 3 times per day for half a year and 1-year follow-ups). Primary endpoints covered incidence of death, nonfatal myocardial infarction (MI), ischemia-driven revascularization, and secondary endpoints included stroke, heart failure, and rehospitalization for ACS. At the same time scores for blood stasis syndrome (BSS) and the incidence of angina pectoris were evaluated before treatment, at month 1, 3, 6, 9, and 12 after treatment. RESULTS: The incidence of ischemia-driven revascularization was obviously less in the treatment group than in the control group (P < 0.05). No patient had nonfatal MI in the treatment group, while 5 patients in the control group had it. The incidence of non-fatal MI showed an obvious lowering tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). Four patients readmitted to hospital in the treatment group, while 12 patients readmitted. There existed obvious tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). The incidence of angina was significantly lower in the treatment group at month 6, 9, and 12 than that at month 1 , but it was lower in the control group at 9 months (P < 0.05). The incidence of angina was 15. 4% in the treatment group, obviously lower than that in the control group (26.2%, P < 0.05). Compared with before treatment, scores for BSS were obviously lowered in the treatment group at 1, 3, 6, 9, and 12 months of treatment and in the control group at 3, 6, 9, and 12 months of treatment (P < 0.05). It was obviously lower in the treatment group than in the control group at 3, 6, 9, and 12 months of treatment (P < 0.01). CONCLUSION: Administration of CHSQABC combined routine Western medicine treatment could reduce the event of revascularization and post-PCI recurrent angina, and improve scores for BSS of ACS patients complicated with DM after PCI.

[Advances in studies on pharmacological action of main chemical constituent of Curcuma Zedoary in preventing in-stent restenosis].

Traditional Chinese medicine Curcuma Zedoary ( E'Zhu) contains essential oil, curcuminoid and other effective constituents, with such pharmacological actions as anti-platelet aggregation, lowing blood lipid, anti-oxidation and anti-inflammation. In recent years, studies have showed that certain extracts and chemical components of E'Zhu could mitigate myocardial cell mitochondria injury and protect vascular endothelium by enhancing heme oxygenase-1 activity, inhibit nuclear factor NF-kappaB, target genes interleukin-associated kinase-1 (IRAK-1), tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), reduce inflammatory infiltration, and inhibit growth factor-induced smooth muscle cells (SMCs) proliferation and migration by impacting oxidation of cellular phosphatases. Due to its different functions in vascular endothelial cells and smooth muscle cells, E'Zhu has been applied in drug-eluting stents, with a potential effect in preventing in-stent restenosis and thrombogenesis. In this paper, studies on pharmacological effects and mechanisms of extracts and main chemical constituents from E'Zhu in preventing vascular restenosis were summarized.

Panax quinquefolium saponin attenuates cardiomyocyte apoptosis and opening of the mitochondrial permeability transition pore in a rat model of ischemia/reperfusion.

AIMS: Opening of the mitochondrial permeability transition pore (mPTP) is a critical event during ischemia/reperfusion (I/R) injury. Recently, we showed that Panax quinquefolium saponin (PQS) alleviates apoptosis of cardiomyocytes by suppressing excessive endoplasmic reticulum stress (ERS) during I/R injury. Here, we hypothesized that this anti-apoptotic effect might be mediated through inhibition of mPTP and the mitochondrial apoptotic pathway. METHODS: Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham, I/R, I/R+PQS (200 mg/kg/d), Cyclosporine A (CsA, 10 mg/kg), I/R+CsA (10 mg/kg), and I/R+PQS+CsA. I/R was modeled in rats by ligating the left anterior descending artery (LAD) for 30 min followed by 120 min of reperfusion. To evaluate the cardioprotective function of PQS, we measured hemodynamics, serum content of creatine kinase-MB (CK-MB), myocardial infarct size, and myocardial apoptotic index (AI). We investigated the underlying mechanism by examining changes in the mitochondrial ultrastructure and membrane potential (ΔΨm), dynamics of mPTP opening, expression of cleaved caspase-3, cleaved caspase-9 in the myocardium, Bcl-2 and Bax in the mitochondria versus cytosol, and translocation of cytochrome c. RESULTS: Administration of PQS to I/R rats significantly reduced serum CK-MB level, infarct size and AI. In addition, PQS protected the mitochondrial structure, markedly inhibited mPTP opening and ΔΨm depolarization, led to upregulation of Bcl-2 and downregulation of Bax in the mitochondria compared to the cytosol, and suppressed the expression of cleaved caspase-9 and cleaved caspase-3, as well as I/R induced translocation of cytochrome c to the cytoplasm. CONCLUSION: Our results show that PQS can alleviate apoptosis of cardiomyocytes during I/R injury, possibly due to repressed mitochondrial apoptotic pathway associated with the opening of mPTP induced by myocardial I/R injury.

[Assessing Chinese herbal medicines for benefiting qi and activating blood circulation in treating unstable angina based on Markov model: a long-term clinical effectiveness exploration].

OBJECTIVE: To assess the long-term clinical effectiveness of Chinese herbal medicines for benefiting qi and activating blood circulation (CHMBQABC) plus routine Western medical intervention in treating unstable angina (UA) patients of qi deficiency blood stasis syndrome (QDBSS) after percutaneous coronary intervention (PCI) based on Markov model. METHODS: A Markov model was established based on prognosis and sequelae of UA patients after PCI treated by CHMBQABC plus routine Western medical intervention or by routine Western medical intervention. According to the transition probabilities of 40 Markov cycles and quality-adjusted life years (QALYs) averagely gained, we assessed the therapeutic advantage of CHMBQABC plus routine Western medical intervention. RESULTS: By the prediction of Markov model for 20 years, the transition probabilities of revascularization, non-fatal myocardial infarction, non-fatal stroke, and all-cause death in the CHMBQABC plus routine Western medical intervention group was 56.65%, 6.53%, 5.16%, and 31.66%, respectively, and the QALYs averagely gained was 12.95; while the transition probabilities of revascularization, non-fatal myocardial infarction, non-fatal stroke, and all-cause death in the Western medical intervention group was 55.31%, 6.87%, 5.25%, and 32.57%, respectively, and the QALYs averagely gained was 12.84. Compared with the Western medical intervention group, the QALYs averagely gained was 0.11 in the CHMBQABC plus routine Western medical intervention group. CONCLUSION: Based on predicted results of the Markov model, CHMBQABC plus routine Western medical intervention got better efficacy in treating UA patients after PCI, indicating CHMBQABC plus routine Western medical intervention could improve the long-term clinical effectiveness for UA patients of QDBSS after PCI.

[Effect of activating blood circulation or activating blood circulation and detoxication on platelet activation, inflammation, and coagulation status in acute myocardial infarction rats].

OBJECTIVE: To observe the effect of activating blood circulation drugs or activating blood circulation and detoxication drugs on indices of platelet activation, inflammation, and coagulation status correlated with blood-stasis and toxin in acute myocardial infarction rats. METHODS: Totally 100 male SD rats were randomly divided into the sham-operation group, the model group, the activating blood circulation group, the activating blood circulation and detoxication group, and the metoprolol group, 20 in each group. Rats in the activating blood circulation group were administered with Xiongshao Capsule at the daily dose of 0.39 g/kg. Rats in the activating blood circulation and detoxication group were administered with Xiongshao Capsule (at the daily dose of 0.39 g/kg) and Huanglian Capsule (at the daily dose of 0.135 g/kg). Rats in the metoprolol group received metoprolol at the daily dose of 2.25 mg/kg. And rats in the rest two groups were administered with normal saline. All medication lasted for 3 successive weeks. After the last administration, the rat model of acute myocardial infarction was prepared by ligation of left anterior descending artery. No ligation was given to rats in the sham-operation group. Animals were sacrificed 24 h after modeling. Tumor necrosis factor-α (TNF-α), ß-thromboglobulin (ß-TG), platelet α granule membrane protein-140 (GMP-140), 11 dehydro-thromboxane B2 (11-DH-TXB2), fibrinopeptide A (FPA), antithrombin III (AT-III), and D-dimer (DD) were detected by ELISA. The mRNA expression of TNF-α was tested by RT-PCR. RESULTS: Platelet activation parameters were significantly increased in the model group, when compared with the sham-operation group (P < 0.01). Compared with the model group, all indices (except GMP-140 in the metoprolol group) obviously decreased in each medicated group (P < 0.01, P < 0.05). Besides, ß-TG and 11-DH-TXB2 were superior in the activating blood circulation and detoxication group to that of the metoprolol group (P < 0.05). But 11-DH-TXB2 was also obviously superior in the activating blood circulation and detoxication group to that of the activating blood circulation group (P < 0.05). Compared with the sham-operation group, an obviously hypercoagulable state was obviously shown in the AMI model group, with significantly increased FPA and DD (P < 0.05 or 0.01) and significantly decreased AT III (P < 0.01). Compared with the model group, the FPA level significantly decreased in each medicated group (P < 0.01), and the AT III level significantly increased in the activating blood circulation group and the activating blood circulation and detoxication group (both P < 0.01). The level of DD obviously decreased in the activating blood circulation and detoxication group (P < 0.01). Besides, the 3 indices were superior in the activating blood circulation and detoxication group to those of the metoprolol group (P < 0.05). Compared with the sham-operation group, the serum TNF-α level and myocardial TNF-α mRNA expression were significantly increased in the model group (P < 0.05, P < 0.01). Compared with the model group, not only the serum TNF-α level was significantly decreased, but also the TNF-α gene expression in the myocardial tissue was improved in the activating blood circulation and detoxication group (P < 0.01). CONCLUSION: Combined use of activating blood circulation and detoxication drugs could play an effective role in treatment of coronary heart disease by fighting against platelet activation, improving the hypercoagulable state, and inhibiting inflammation, which was significantly better than using activating blood circulation and removing stasis drugs alone.

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Associations between remnant cholesterol levels and mortality in patients with diabetes.

BACKGROUND: Dyslipidemia is frequently present in patients with diabetes. The associations of remnant cholesterol and mortality remains unclear in patients with diabetes. AIM: To explore the associations of remnant cholesterol with all-cause and cardiovascular mortality in patients with diabetes. METHODS: This prospective cohort study included 4740 patients with diabetes who participated in the National Health and Nutrition Examination Survey from 1999 through 2018. Remnant cholesterol was used as the exposure variable, and all-cause and cardiovascular mortality were considered outcome events. Outcome data were obtained from the National Death Index, and all participants were followed from the interview date until death or December 31, 2019. Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes, in which remnant cholesterol was modeled as both a categorical and a continuous variable. Restricted cubic splines (RCSs) were calculated to assess the nonlinearity of associations. Subgroup (stratified by sex, age, body mass index, and duration of diabetes) and a series of sensitivity analyses were performed to evaluate the robustness of the associations. RESULTS: During a median follow-up duration of 83 months, 1370 all-cause deaths and 389 cardiovascular deaths were documented. Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality [hazard ratio (HR) 95% confidence interval (CI): 0.66 (0.52-0.85)]; however, when remnant cholesterol was modeled as a continuous variable, it was associated with increased risks of all-cause [HR (95%CI): 1.12 (1.02-1.21) per SD] and cardiovascular [HR (95%CI): 1.16 (1.01-1.32), per SD] mortality. The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality. Subgroup and sensitivity analyses did not reveal significant differences from the above results. CONCLUSION: In patients with diabetes, higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality, and diabetes patients with slightly higher remnant cholesterol (0.68-1.04 mmol/L) had a lower risk of all-cause mortality.

[Fluctuant hypertension and platelet activation: current situations and control strategies with integrative medicine].

In recent years a huge amount of clinical studies have proved that fluctuant hypertension could aggravate the damage of target organs and increase the incidence of acute cardio-/cerebrovascular events, when compared with stable hypertension [increased mean artery blood pressure (MBP)]. How to prevent and treat fluctuant hypertension and its damage of target organs has become one of the hot and difficult problems in the field of hypertension studies all over the world. Hypertensive patients often suffer from thromboembolic target organ damage. Platelet activation plays a key role in this progress, but its concrete mechanisms have not been clearly clarified. Based on the in-depth discussions on progress of fluctuant hypertension, its relationship with platelet activation and blood stasis syndrome of Chinese medicine (CM) in recent three years, we proposed, under the fluctuant hypertensive state, the prethrombotic state has occurred in the organisms, i.e., a pathological state featured by platelet activation, liable to have vulnerable thrombopoiesis, and accompanied by endothelial dysfunction. Blood stasis syndrome might occupy an important position in CM syndrome typing of fluctuant hypertension. Herbs for activating blood circulation and removing stasis might have an extensive application prospect.

[Diagnostic standard evaluation of Chinese medicine syndrome for coronary heart disease patients after percutaneous coronary intervention].

OBJECTIVE: To evaluate the validity, reliability, and clinical applicability of Chinese medicine syndrome diagnostic standards for coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI), which was established by expert consultation. METHODS: A total of 1 050 CHD patients after PCI were recruited from 23 hospitals. The sensitivity, specificity, accuracy, positive likelihood ratio, and area under ROC curve were used to evaluate the validity of diagnostic standards for Chinese medical syndrome types. The observable agreement rate and Kappa value were used to evaluate the reliability. Positive predictive value and negative predictive value were used to evaluate the clinical applicability. RESULTS: The sensitivity, specificity, accuracy, positive likelihood ratio, area under ROC curve, observable agreement rate, Kappa value, positive predictive value, and negative predictive value of each Chinese medicine syndrome in CHD patients after PCI were as follows: 95.26%, 93.70%, 94.86%, 15.13, 0.924, 98.76%, 0.969, 97.76%, and 87.24% for blood stasis syndrome; 96.42%, 95.34%, 96.00%, 20.70, 0.957, 99.52%, 0.990, 97.02%, and 94.42% for qi deficiency syndrome; 88.19%, 96.46%, 94.19%, 24.89, 0.923, 96.67%, 0.915, 90.39%, and 95.58% for phlegm turbidity syndrome; 91.06%, 98.77%, 97.05%, 74.22, 0.950, 98.67%, 0.960, 95.54%, and 97.46% for cardiac blood stasis syndrome; 98.41%, 96.73%, 97.33%, 30.10, 0.976, 98.86%, 0.976, 94.40%, and 99.09% for qi deficiency blood stasis syndrome; 94.81%, 94.75%, 94.76%, 18.07, 0.948, 97.71%, 0.918, 72.73%, and 99.20% for phlegm-stasis stagnation syndrome. CONCLUSION: The validity, reliability, and clinical applicability of Chinese medicine syndrome diagnostic standards for CHD patients after PCI were rational and considerable in clinical practice.

[Association study between Chinese medicine blood stasis syndrome and TIMI risk stratification of patients with unstable angina pectoris].

OBJECTIVE: To study the correlation between thrombolysis in myocardial infarction (TIMI) risk stratification and blood stasis syndrome (BSS) score in patients with unstable angina pectoris (UAP), and to analyze the relation of BBS degree and UAP clinical outcomes. METHODS: Collected were general data, demographic data, risk factors, Chinese medical symptoms and syndromes, coronary artery angiography results, relevant physical and chemical examinations from 114 UAP inpatients. Gensini score, TIMI risk score, and BSS score of these patients were calculated. RESULTS: The BBS score and Gensini score were significantly positively correlated (r = 0.78, P < 0.01). The BBS score was significantly higher in those with lesion in three branches than those with lesion in one branch or in two branches (P < 0.05). The BBS score was significantly higher in the high risk group than in the lower risk group and the medium risk group (P < 0.01). The TIMI risk score was obviously higher in the severe blood stasis group than in the moderate blood stasis group and the mild blood stasis group (P < 0. 05, P < 0.01). The BBS score and TIMI risk score was positively correlated (r = 0.23, P < 0.05). CONCLUSION: The BBS score was positively correlated with more coronary arteries involved. The more severe BBS degree, the TIMI risk score more higher, and the BBS degree more syndrome.

Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme.

INTRODUCTION: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. Results：The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.