ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction， and their regulatory role in mitophagy. MethodsSixty male C57BL/6 mice were randomly assigned to six groups： sham-operated group， model group， Qingxin Jieyu granules low-， medium-， and high-dose groups （1.3， 2.6， 5.2 g·kg^-1）， and sacubitril valsartan sodium group （0.03 g·kg^-1）， with 10 mice per group. Except for the sham-operated group， all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters， including end-diastolic and end-systolic diameters （LVIDd， LVIDs）， diastolic and systolic posterior wall thickness （LVPWd， LVPWs）， end-diastolic and end-systolic volumes （LV Vold， LV Vols）， left ventricular ejection fraction （LVEF）， and fractional shortening （LVFS）. Additionally， the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify brain natriuretic peptide （BNP）， creatine kinase isoenzyme （CK-MB）， angiotensinⅡ （AngⅡ）， and lactate dehydrogenase （LDH） levels in the serum of mice. Histological analysis using hematoxylin-eosin （HE） and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors， including basic fibroblast growth factor （bFGF） and vascular endothelial growth factor （VEGF）. Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase （p-AMPK） and phosphorylated mammalian target of rapamycin （p-mTOR） proteins in myocardial tissue from each experimental group. ResultsCompared to the sham-operated group， the model group mice exhibited significantly elevated levels of LV Vold， LV Vols， LVIDd， LVIDs， cardiac mass index， heart weight/tibia length ratio， BNP， LDH， and p-mTOR protein expression （P<0.05）， along with decreased levels of LVPWd， LVPWs， LVEF， LVFS， and p-AMPK protein expression （P<0.05）. The model group also displayed substantial inflammatory cell infiltration， collagen deposition in myocardial cells， reduced expression of bFGF and VEGF， mitochondrial swelling， and cristae fragmentation. Compared to the model group， the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs， LV Vold， LV Vols， BNP， CK-MB， LDH， and p-mTOR protein expression （P<0.05）， coupled with increases in LVEF， LVFS， and p-AMPK expression （P<0.05）. Improvements were observed across all treatment groups， including reduced inflammatory cell infiltration and collagen deposition， increased bFGF and VEGF expression， alleviated mitochondrial swelling， and the presence of autophagosomes and lysosomes. ConclusionThe results show that Qingxin Jieyu granules can regulate mitochondrial autophagy in myocardial tissue and inhibit ventricular remodeling to improve cardiac performance， by up-regulating the p-AMPK expression in the myocardial tissue of mice with ventricular remodeling after myocardial infarction， and down-regulating the p-mTOR expression.

Based on the natures and flavors of herbal medicinals recorded in Shen Nong's Classic of the Materia Medica （《神农本草经》）； Miscellaneous Records of Famous Physicians （《名医别录》）， this study analyzed the characte-ristics of the natures， flavors and combination of medicinals of the two-herb compound formulas in Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）.Finally， 31 compound formulas were included， and it was found that the nature and flavor of the herbs in these two-herb compound formulas are closely related to the functions of the compound formulas， such as the common pairing of the acrid and the sweet herbs to warm yang and transform qi， the acrid and the bitter herbs in pairs to regulate and harmonize cold and heat， the sweet and the bitter in pairs to remove dampness and clear heat， the acrid and the acrid in pairs to arrest vomiting and direct qi downward， and the sour and the sweet in pairs to slow the urgent and relieve pain. Regardless of the deficiency or excess nature of the disease， the corresponding two-herb compound formulas often aim to reinforce healthy qi while eliminating pathogenic factors， with some formulas showcasing a unique correspondence between the disease pattern and the symptoms addressed.

Ventricular remodeling is a crucial pathological process in the prognosis and regression of myocardial infarction. Guided by the theory of “yang transforms into qi， while yin constitutes form" of The Inner Canon of Yellow Emperor （《黄帝内经》）， combined with the pathological characteristics and manifestations of ventricular remodelling， it is believed that insufficient "yang transforms into qi" and excess "yin constitutes form" resulting to heart yang deficiency and turbid pathogen obstruction are the basic pathomechanism of ventricular remodelling after myocardial infarction； insufficient "yin constitutes form" and excess "yang transforms into qi" resulting to inadequate nourishment of the heart meridians and the emergence of various pathological changes are the key pathomechanism of prognosis and regression. Combined with clinical practice， we advocated that harmonizing yin and yang to maintain the dynamic balance of "yang transforms into qi" and "yin constitutes form". We also proposed the use of warming and tonifying to harmonise qi and transform it to help yang transport； resolving phlegm and removing dampness， invigorating blood and resolving toxins to disperse yin accumulation； clearing heat and extinguishing wind， and nourishing yin and channels to improve the prognosis. All these findings and summary could provide ideas on traditional Chinese medicine for prevention and treatment of ventricular remodelling after myocardial infarction.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Aim To study the causal relationship between coffee consumption and atherosclerosis risk.Methods Based on the public genome database IEU Open GW AS project website,relevant data were obtained,and in-strumental variables closely related to exposure and outcome were screened.Mendelian randomization analysis was per-formed using the inverse variance weighted method,weighted median method,and MR Egger method to assess the causal relationship between coffee consumption and arteriosclerosis(including coronary atherosclerosis,peripheral atherosclerosis,cerebral atherosclerosis,and other atherosclerosis).In addition,the Egger intercept method was used to detect the level of pleiotropy,the Cochran Q test was used to assess the heterogeneity,and the leave one out method was used to perform sensitivity analysis,so as to ensure the robustness of the results.Results The study showed that the F-values of the instrumental variables included in the study were all greater than 10,and there was no weak instrumental variables bias.Coffee consumption was positively correlated with the risk of coronary atherosclerosis(OR=1.535 5,95％CI=1.108 4～2.127 2,P=0.009 9),peripheral atherosclerosis(OR=2.098 6,95％CI=1.182 2～3.725 7,P=0.011 4),and other atherosclerosis(OR=1.864 7,95％CI=1.052 9～3.302 4,P=0.032 6),but not with the risk of cerebral atherosclerosis.Heterogeneity test Q_pval＞0.05,level pleiotropy test interval P＞0.05.Conclusions The single nucleotide polymor-phisms selected in the study are all strong instrumental variables,and there is no heterogeneity or horizontal pleiotropy,in-dicating reliable results.The research shows that coffee consumption increases the risk of coronary atherosclerosis,pe-ripheral atherosclerosis and other atherosclerosis,and has no significant correlation with the risk of cerebral atherosclerosis.The health management of atherosclerosis patients should reduce coffee consumption.

Objective To observe the influence of routine statins drugs combined with Guanxin Danshen (Coronary Salvia Root)Gutta Pills and Chuanxinlian(Andrographitis)Tablet on serum inflammatory markers and blood fat in patients with acute coronary syndrome(ACS)after percutaneous coronary inter-vention(PCI).Methods ACS patient(n=40)were randomly divided into control group and treatment group(each n=20)after PCI.The control group was treated with basic therapy of Western medicine and statins,and treatment group was additionally given Guanxin Danshen Gutta Pills and Chuanxinlian Tablet for 30 d.The levels of serum high sensitivity C-reactive protein(hs-CRP), tumor necrosis factor-α (TNF-α)and blood fat were detected by using ELISA,and integrals of blood stasis pattern were calculat-ed.Results The levels of hs-CRP and TNF-αdecreased significantly in 2 groups after treatment(P<0.05 or P<0.01), and difference between 2 groups had statistical significance after treatment(P<0.01).The level of serum total cholesterol(TC)decreased significantly and level of high-density lipo-protein-cholesterol(HDL-C increased in treatment group(P<0.05).The integrals of blood stasis pat-tern decreased significantly in treatment group after treatment(P<0.01).Conclusion Guanxin Dan-shen Gutta Pills and Chuanxinlian Tablet,with effects of activating blood and removing toxicity,can fur-ther reduce the levels of inflammatory markers, hs-CRP and TNF-α, relieve blood stasis and assist to control blood fat in patients with ACS after PCI.

With the development of modern technology and clinical practice,the classic randomized controlled trial nowadays cannot meet the researchers' needs for evidence with more reliable external validity,especially in the field of TCM.Meanwhile,real-world study (RWS) has been attracting more attention and at the forefront of clinical research all over the world for providing evidence in conformity with the real world condition.In this paper,we firstly described the basic concept of RWS,and then found that it was characterized by large representative samples,loose inclusion or exclusion criteria,allocation of interventions according to patients conditions and willingness,long-term follow-up,and clinically relevant endpoints.By analyzing the existing examples of RWS,we noted and discussed the promising future of RWS in TCM clinical research.Finally,we hope this paper will provide some inspiration for TCM researchers.

The study used questionnaires to investigate clinical TCM master degree students who enrolled in the year of 2011 and 2012 about the implementation effect of training plan before and after standardization of resident training. The results showed that a lot of students in the year 2011 and 2012 were satisfied with their training plan and training mode. However, the ability of clinical skills and academic research improved much higher after standardization of resident training among the students in 2012. The study showed that our education training plan met the training goal and reflected achievements in the cultivation of medical master degree of TCM. The training plan and training mode were higher satisfied for the students in the year 2011 and 2012. The conception of tutor, training target, the relationship between clinical skills and scientific research should be improved in future.