The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway / 中医杂志

ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

Experimental Research Progress of Replenishing Qi and Activating Blood Circulation Traditional Chinese Medicine on Mitochondrial Quality Control in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.

Role of plasma C-reactive protein in predicting in-stent restenosis in patients with stable angina after coronary stenting / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of plasma high sensitivity C-reactive protein (hs-CRP) in in-stent restenosis (ISR) remains controversial. We investigated plasma hs-CRP level at both admission and follow-up in patients with stable angina (SA) after successful coronary stenting in order to clarify the predictive value of hs-CRP for ISR.</p><p><b>METHODS</b>We summarized 303 consecutive chronic SA patients with coronary drug-eluting stent (DES) implantation. The ISR was analyzed by quantitative coronary analysis (QCA) at a mean follow-up of 8 months, and the patients were divided into two groups according to the detected ISR as ISR group (n = 48) and non-ISR group (n = 255). Plasma hs-CRP was examined at both admission and 8-month follow-up in all patients, standard medication continued throughout the investigation period.</p><p><b>RESULTS</b>QCA presented that 48 patients (15.8%) suffered from ISR at follow-up. The basic clinical characteristics were similar between the two groups, while plasma hs-CRP was higher in ISR group than that in non-ISR group at both admission and follow-up, P < 0.001 respectively. Multivariate regression analysis indicated that plasma hs-CRP level at either admission or follow-up could independently predict ISR occurrence (OR = 5.581, 95%CI 2.532-12.302, P < 0.001 and OR = 6.299, 95%CI 2.722-14.577, P < 0.001, respectively).</p><p><b>CONCLUSIONS</b>Our data indicate that plasma hs-CRP level may independently predict ISR at both admission and follow-up in SA patients with coronary DES implantation, which implies that a chronic, sustained systemic inflammatory response might be involved in ISR pathogenesis.</p>

Increased plasma C-reactive protein level predicts rapid progression of non-target atherosclerotic lesions in patients with stable angina after stenting / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although the role of C-reactive protein (CRP) in predicting rapid progression of atherosclerotic lesions has been intensively studied in unstable coronary artery disease, the data from patients with stable angina (SA) are largely absent. The present study evaluated a middle-size patient cohort who underwent percutaneous coronary intervention (PCI) with stent implantation and follow-up coronary angiography (CAG) and tested the hypothesis that increased plasma level of high-sensitive CRP would indicate rapid progression of de novo non-target coronary artery lesions in Chinese patients with SA.</p><p><b>METHODS</b>The study population comprised of 311 consecutive patients with chronic SA who underwent coronary stent implantation on initial admission and angiographic follow-up ((8.5 ± 1.2) months). Rapid angiographic progression of non-target lesion was angiographically assessed and the patients were classified into two groups according to whether the progression existed or not. The relation of plasma CRP levels to the progression of atherosclerosis was investigated.</p><p><b>RESULTS</b>Baseline demographic, clinical, and angiographic data were similar in patients with and without progression. Rapid angiographic progression of non-target lesions occurred in 136 patients (43.7%) at follow-up: 77 had a ≥ 10% diameter reduction of pre-existing stenosis ≥ 50%, 26 had a ≥ 30% diameter reduction of a pre-existing stenosis < 50%, 64 developed a new lesion ≥ 30% in a previously normal segment, and 4 had progression of a lesion to total occlusion. Progression of non-target lesions was not associated with target lesion restenosis formation. High-sensitive CRP levels were markedly higher in progression patients than in non-progression ones (1.60 (0.80 - 3.46) mg/L vs. 0.96 (0.55 - 1.87) mg/L, P < 0.001). Multivariate regression analysis showed that plasma CRP independently predicted rapid angiographic progression of non-target lesions (P = 0.001). High-sensitive CRP levels above 1.32 mg/L (the cutoff value) were associated with a 3.5-fold increase in the risk of developing rapid atherosclerotic progression (OR = 3.497, 95%CI 2.045 - 5.980).</p><p><b>CONCLUSION</b>The data confirmed and extended previous studies that plasma CRP might independently predict non-target lesion progression in patients with SA after stent implantation.</p>

Angiographic prevalence of myocardial bridging in a defined very large number of Chinese patients with chest pain / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Muscle fibers overlying the intramyocardial segment of an epicardial coronary artery are termed myocardial bridging (MB). Variable prevalence of MB has been described at autopsy and angiographic series with small and large sample size studies. In addition, no similar study was reported in Chinese population. The aim of this study was to investigate the angiographic prevalence of MB in consecutive 37,106 Chinese patients with chest pain from our center.</p><p><b>METHODS</b>We conducted an observational study to evaluate the consecutive cases with MB among patients undergone selective coronary angiography, and analyzed the angiograhic prevalence and clinical features of MB in this study of very large sample size.</p><p><b>RESULTS</b>Among 37 105 patients with chest pain we found 1002 cases with 1011 MBs in a retrospective manner, and the overall prevalence was 2.70%. Although more than 99% (991/1002) of patients had single bridge, 8 cases were found to have more than two MBs (seven with two, and one with three). Altogether 54.39% of cases (545/1002) had MB without atherosclerotic lesions, and 96.24% (973/1011) of bridging located in the left anterior descending coronary artery (LAD), mainly in the middle of LAD (792/1011, 78.33%). According to Nobel classification, of the single bridge (n=991), <50% of obstruction was predominant (471/991, 47.52%). Totally 50%-69% accounted for 34.81% (345/991), >70% of obstruction was 17.65% (175/991).</p><p><b>CONCLUSIONS</b>These data showed that the prevalence of angiographically detectable MB in Chinese patients with chest pain was similar to those of the previous studies, with 2.7% prevalence in this very large sample size.</p>

Effects of sirolimus-eluting stent on calcified coronary lesions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Calcified coronary lesions carry the risk of suboptimal stent expansion, subsequently leading to restenosis. The effectiveness of sirolimus-eluting stents (SES) for the treatment of calcified lesion has not been fully investigated. In the present study, therefore, we evaluated the effectiveness of SES implantation for the treatment of calcified coronary lesions.</p><p><b>METHODS</b>A total of 333 consecutive patients with 453 lesions were enrolled in this study. They were divided into two groups according to whether the lesion treated with SES was calcified or not; no calcification group (n = 264) and calcification group (n = 189). Lesions treated with SES were subjected to quantitative coronary angiography (QCA) immediately and 8 months following stenting.</p><p><b>RESULTS</b>Baseline clinical, demographic or angiographic characteristics were well balanced in both groups. Angiographic follow-up at 8 months, the in-stent restenosis and in-segment restenosis rates were not significantly different between the two groups; in-stent restenosis: 3.8% vs 4.2%; P = 0.081; in-segment restenosis: 8.7% vs 10.6%, P = 0.503. The target lesion revascularization (TLR) was also not significantly different between the two groups; 4.9% vs 6.9%, P = 0.378. In addition, the in-stent late loss was similar in both groups; (0.16 +/- 0.40) mm vs (0.17 +/- 0.33) mm, P > 0.05. Meantime, overall thrombosis rates were also similar in both groups; 1.6% vs 1.6%, P > 0.05.</p><p><b>CONCLUSION</b>Although calcified coronary lesion was hard to stent, successful percutaneous coronary intervention with SES stenting for calcified lesions was conferred by the similar favorable results that were seen when comparing non-calcified and calcified coronary lesions.</p>

Age-based clinical and angiographic outcomes after sirolimus-eluting stent implantation in patients with coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Advanced age independently predicts early and late mortality and major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI). Randomized clinical trials indicate that sirolimus-eluting stent (SES) implantation reduces target lesion revascularization (TLR), but there are limited data on the impact of age on outcomes following SES implantation in patients with coronary artery disease (CAD) in real-world practice.</p><p><b>METHODS</b>A total of 333 CAD patients with 453 lesions were enrolled in this study. Subjects were divided into two groups according to age: a young group (< 65 years old, 244 patients with 369 lesions) and elderly group (= 65 years old, 89 patients with 113 lesions). Clinical follow-up and quantitative coronary angiography (QCA) were performed seven months after PCI.</p><p><b>RESULTS</b>Baseline clinical, demographic, angiographic, and procedural chararcteristics were similar in both groups, except that there were more female patients in the elderly group (21.3% vs 9.8%, P = 0.006). Primary success rate was similar in both groups (96.5% in young group vs 95.7% in elderly group, P > 0.05). During angiographic follow-up at 7 months, binary in-stent restenosis and in-segment restenosis rates were not significantly different between the two groups (4.7% vs 1.8%; 9.7% vs 8.8%, P > 0.05 respectively). Both sub-acute and late thrombosis rates were similar in the two groups (0.3% vs 0.9% and 1.2% vs 0.9%, P > 0.05 respectively). TLR was not significantly different between the two groups (6.5% vs 3.5%; P = 0.246). The rates of bleeding, stroke, angina rehospitalization during the follow-up period were also similar in both groups (P > 0.05 respectively).</p><p><b>CONCLUSION</b>Despite a high-risk clinical profile, coronary SES implantation can be safely and effectively performed in elderly patients with a similar procedural success rate, a low complication rate, and excellent 7-month outcomes.</p>

Drug-eluting stent for the treatment of small coronary lesion: comparison between sirolimus- and paclitaxel-eluting stent / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with small coronary lesions are at increased risk for repeat interventions after coronary angioplasty and stenting. The efficacy of drug-eluting stents (DES) has been demonstrated to improve the outcomes of these patients and is a focus of interest. Currently, two platforms of DES are available (sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES)). However, it has less been known that DES, SES vs PES, is superior for the treatment of small coronary lesions.</p><p><b>METHODS</b>In this retrospective study, 87 consecutive patients with 151 lesions underwent implantation of coronary SES (n = 68) and PES (n = 83). Quantitative coronary angiography (QCA) was performed at the time of stent implantation and subsequently at 8 months post-stenting. Small vessel disease was defined as lesions in vessels with diameter 2.5 mm measured by QCA. Major adverse cardiac events (MACE) including death, thrombosis, nonfatal myocardial infarction and target lesion revascularization (TLR) were compared between the two groups.</p><p><b>RESULTS</b>Baseline clinical characteristics and angiographic parameters were similar between the two groups. At clinical and angiographic follow-up, overall thrombosis rates were similar in both groups (0 vs 1.2%, P > 0.05). The TLR and in-segment restenosis were not significantly different (19.1% vs 25.3%; 10.3% vs 10.8%, P = 0.365 and P = 0.913 respectively) between the two groups. The in-stent restenosis rate, however, was significantly higher in the PES group (4.4% vs 21.7%; P = 0.002). Similarly, the late loss was significantly higher in the PES group ((0.140.38) mm vs (0.490.61) mm; P < 0.001).</p><p><b>CONCLUSIONS</b>In this small sample-size, non-randomized study, the data indicated that implantation of SES for the treatment of patients with small coronary lesion showed more favorable results in respect of restenosis compared with PES implantation.</p>

A comparison of clinical and angiographic outcomes after Excel bioabsorbable polymer versus Firebird durable polymer rapamycin-eluting stent for the treatment of coronary artery disease in a "real world" setting: six-month follow-up results / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several clinical trials have shown that rapamycin-eluting stents significantly reduce the risk of restenosis after percutaneous coronary intervention (PCI). The Firebird stent and the Excel stent (coated with bioabsorbable polymer) are two different types of rapamycin-eluting stents made in China, both have been recently approved for clinical use in China by State Food and Drug Administration. However, it is unclear whether there are differences in safety and efficacy between the two types of stents in daily practice.</p><p><b>METHODS</b>In the month of June 2006, a total of 190 consecutive patients were treated exclusively with Firebird stents (n = 93, Firebird group) or Excel stents (n = 97, Excel group) in our center and were included in this study. The frequency of major adverse cardiac events (MACE, a composite of death, myocardial infarction or target lesion revascularization), binary restenosis, and late lumen loss and stent thrombosis during a six-month follow-up period were compared between the two groups.</p><p><b>RESULTS</b>Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low in hospital and at 6 months (2.1% in the Excel group and 0% in the Firebird group, P > 0.05). The 6-month angiographic in-stent restenosis rate was 0% in both groups, with an associated late loss of (0.15 +/- 0.21) mm versus (0.14 +/- 0.20) mm (P = 0.858) and the in-segment restenosis rate was also 0% for the Excel group and the Firebird group. There was no definite stent thrombosis identified in either group during the six-month follow-up period and only one patient in the Excel group had probable stent thrombosis in hospital.</p><p><b>CONCLUSIONS</b>Results from this mid-term, single-center study showed that both of the Firebird and the Excel rapamycin eluting stent had similar effects on reducing the incidence of MACE and the risk of restenosis (both in-stent and in-segment binary restenosis) after PCI in daily practice.</p>

A comparison of angiographic and clinical outcomes after sirolimus-eluting versus paclitaxel-eluting stents for the treatment of in-stent restenosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In-stent restenosis (ISR) remains a challenge for interventional cardiologists. Some data suggest that drug-eluting stents (DES) represent a promising new option for the treatment of patients with ISR. Currently, 2 DES platforms are available [sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES)], but the superiority of either approach for treating ISR has not been convincingly demonstrated. The aim of the present study was to retrospectively compare angiographic and clinical outcomes after treatment of ISR with SES or PES in a series of consecutive patients with ISR.</p><p><b>METHODS</b>A total of 745 consecutive patients were treated with bare metal stents from April 12, 2004 to December 31, 2004 in our center. Of these, clinically driven target lesion revascularization (TLR) was performed in 54 ISR from 54 patients at 7 months. Of the 54 patients with ISR, 36 received SES and 18 received PES. Follow-up included angiography and assessment of clinical outcome, both performed 7 months after DES implantation.</p><p><b>RESULTS</b>There were no significant differences in baseline clinical data (including medication usage and lesion characteristics) between the two groups. Except for overlapping of multiple stents, procedural parameters were also similar in both groups. Seven-month angiographic follow-up showed that the binary restenosis rate was higher in patients treated with PES than that in patients treated with SES (in-stent binary restenosis: 27.8% vs 5.6%, P < 0.023; In-segment binary restenosis: 44.4% vs 13.9%, P < 0.014). Major adverse cardiac events (MACE) occurring during hospitalization or during the follow-up period including thrombosis and TLR was similar in both groups (22.2% vs 8.3%, P > 0.05).</p><p><b>CONCLUSIONS</b>Results from this small sample size, retrospective, single-center study showed that SES might be superior to PES in treating ISR because of lower 7-month restenosis rates (both in-stent and in-segment binary restenosis) with no increased incidence of MACE.</p>

A single center investigation of bare-metal or drug-eluting stent restenosis from 1633 consecutive Chinese Han ethnic patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stents are widely used in China but the clinical impression is somehow that restenosis is less common because of the lower prevalence of coronary artery disease (CAD) and associated risk factors in Chinese populations. However, no large-sample published studies are available on angiographic stent restenosis including those of bare-metal stent (BMS) or drug-eluting stent (DES) in Chinese Han ethnic population.</p><p><b>METHODS</b>A total of 1633 consecutive patients with CAD who had undergone coronary stenting, quantitative coronary angiography (QCA) were retrospectively studied. At the time of stent implantation and at 7 months post-stenting 675 patients had a follow-up angiography. Statistical analysis was made with the chi-square test for categorical variables, unpaired t test for continuous variables, univariate or multivariate regression for baseline and angiographic characteristics and the Kaplan-Meier method for rate of target lesion revascularization (TLR).</p><p><b>RESULTS</b>Stent restenosis was defined as > or = 50% diameter stenosis in the dilated segment. A total of 675 patients with 1074 lesions were subjected to angiographic follow-up for 7 months on average. Of these lesions, 448 were implanted with BMS whereas 626 lesions with DES. At 7 months, bare-metal in-stent restenosis occurred in 148 lesions (33.0%), and bare metal in-segment restenosis in 155 lesions (34.6%) in contrast to drug-eluting in-stent restenosis in 48 lesions (7.7%) and drug-eluting in-segment restenosis in 73 lesions (11.7%) (P < 0.001 compared with BMS respectively). Late loss in both in-stent and in segment was higher in BMS than in DES groups [(1.00 +/- 0.69) vs (0.28 +/- 0.52); (0.78 +/- 0.71) vs (0.21 +/- 0.52), P < 0.001 respectively]. Angulated lesion, lesion length, pre-procedural minimal luminal diameter (MLD), and BMS were independent predictors for TLR, (P < 0.01 respectively), whereas current smoker, ostial lesion, and stent overlapping, post-procedure in-stent MLD, lesion length, and stent types were independent predictors for in-segment restenosis (P < 0.01 respectively). Standard coronary risk factors such as hypertension, hyperlipidemia, diabetes, and history of CAD were not associated with a higher rate of restenosis caused by BMS or DES implantation in our Chinese Han ethnic population.</p><p><b>CONCLUSIONS</b>Coronary stenting including BMS or DES implantation in Chinese Han ethnic patients is associated with a restenosis rate comparable to that demonstrated in previous studies from the western countries, and predictors of stent restenosis are somehow different from those in the western population.</p>