ObjectiveTo investigate the effects and potential mechanisms of Tongmai Yangxin Pills （通脉养心丸） （TYPs） in preventing ischemia-reperfusion （I/R）-induced arrhythmia. MethodsSixty male SD rats were randomly assigned to sham operation group， model group， amiodarone group， low-dose and high-dose TYPs group， with 12 rats in each group. The sham operation group and the model group received 10 g/（kg·d） normal saline by gavage， the amiodarone group received 60 mg/（kg·d） amiodarone， and the low-dose and high-dose TMP groups received 1 g/（kg·d） and 2 g/（kg·d） TYPs solution respectively， for 21 days， administered twice daily. On the day after the last administration， the I/R model was established in the model and medication groups by ligation of the left anterior descending coronary artery with a cannula， while the sham operation group underwent the same procedure without ligation. Electrocardiogram recordings were continuously monitored throughout the modeling process. Heart rate was recorded at five time points， before ischemia （t-0）， 5-10 min after ischemia （t-1）， 10-15 min after ischemia （t-2）， 15-30 min after ischemia （t-3）， and during the first 2 min of reperfusion （t-4）； the incidence of arrhythmia including ventricular premature beats （VPB）， ventricular tachycardia （VT）， and ventricular fibrillation （VF） was recorded； arrhythmia scores were calculated. After 24 hours of reperfusion， left ventricular myocardial tissue was collected. Hematoxylin-eosin （HE） staining was performed to observe pathological changes. RT-PCR was used to detect the mRNA expression of microRNA-1 （miRNA-1）， microRNA-133a （miRNA-133a）， and potassium （K⁺） and calcium （Ca²⁺） ion channel-related genes including KCND2， KCNH2， KCNE2， KCNQ1， KCNE1， KCNJ2， CACNA1C， and CACNB1. Western blot analysis was used to measure protein levels of transient outward potassium current protein （Kv4.2）， rapidly activating delayed rectifier potassium current protein （HERG）， slowly activating delayed rectifier potassium current protein （KvLQT1）， inward rectifier potassium current protein （Kir2.1）， and L-type calcium channel protein （Cav1.2）. ResultsCompared with sham operation group， the model group showed diffuse myocardial hemorrhage， inflammatory cell infiltration， myocardial necrosis， nuclear pyknosis， vacuolar degeneration， and disrupted myocardial fibers； the model group also exhibited a decreased heart rate （t-1 to t-4）， increased arrhythmia scores， elevated miRNA-1 and miRNA-133a expression， and decreased mRNA expression of KCND2， KCNH2， KCNE2， KCNQ1， KCNE1， KCNJ2， CACNA1C， and CACNB1 in myocardial tissue； additionally， Kv4.2， HERG， KvLQT1， Kir2.1， and Cav1.2 protein levels significantly reduced （P＜0.01）. Compared to the model group， all medication-treated groups showed reduced myocardial damage， including less hemorrhage， reduced inflammatory infiltration， and improved myocardial structure， with the high-dose TYPs group exhibiting the most significant improvement； the amiodarone group and high-dose TYPs group showed a significant increase in heart rate （t-1 to t-4）， lower arrhythmia scores， reduced miRNA-1 and miRNA-133a expression； the high-dose TYPs group exhibited significantly increased mRNA expression levels of KCND2， KCNH2， KCNQ1， KCNJ2， and CACNA1C， as well as elevated protein levels of Kv4.2， HERG， KvLQT1， Kir2.1， and Cav1.2 （P＜0.05 or P＜0.01）. ConclusionTMPs can improve myocardial damage and reduce the incidence of ventricular arrhythmia in I/R rats. The underlying mechanism may be related to the downregulation of miRNA-1 and miRNA-133a gene expression， as well as the upregulation of K⁺ and Ca²⁺ channel-related genes and proteins.

ObjectiveTo evaluate the clinical effectiveness and safety of Modified Zhigancao Granules （炙甘草汤加味颗粒） for preventing the early recurrence following radiofrequency ablation in patients with atrial fibrillation （AF） of qi-yin deficiency syndrome. MethodsA multi-center， randomized， double-blind， placebo-controlled trial was designed. A total of 116 patients with atrial fibrillation of qi-yin deficiency syndrome who underwent radiofrequency ablation for the first time were enrolled from 3 centers， and they were randomly divided into a treatment group （59 cases） and a control group （57 cases）. Both groups received basic western medicine treatment after surgery. In addition， the treatment group was given oral Modified Zhigancao Granules， while the control group was given oral placebo granules. The dosage for both groups was 20 g each time， twice a day， with continuous treatment for 12 weeks. The recurrence of atrial fibrillation in both groups was recorded at 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery. The serum levels of B-type natriuretic peptide （BNP）， interleukin-6 （IL-6）， high-sensitivity C-reactive protein （hs-CRP）， and tumor necrosis factor-α （TNF-α） were detected before treatment and 12 weeks after treatment in both groups. The scores of Atrial Fibrillation Effect on QualiTy-of-life （AFEQT） Questionnaire （including scores of the daily life dimension， symptom dimension， treatment worry dimension， treatment satisfaction dimension， and total score） and traditional Chinese medicine （TCM） syndrome scores were compared before treatment and at 4 weeks， 8 weeks， and 12 weeks between groups. Safety indicators such as blood routine， urine routine， liver function， and renal function were monitored before and after treatment. ResultsNine of the treatment group and seven of the control group dropped out. Finally， 50 patients in each group were included in the statistical analysis. At 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery， the recurrence rates of AF in the treatment group were 2.0% （1/50）， 2.0% （1/50）， 4.0% （2/50）， and 10.0% （5/50）， respectively； while those in the control group were 2.0% （1/50）， 26.0% （13/50）， 28.0% （14/50）， and 34.0% （17/50）， respectively. Compared with the control group at the same time points， the early recurrence rates of AF in the treatment group were significantly lower at 4 weeks， 8 weeks， and 12 weeks after surgery （P＜0.01）. Compared with the baseline within group， BNP， hs-CRP， IL-6， and TNF-α in the treatment group all decreased after 12 weeks of treatment （P＜0.05）； the difference in hs-CRP levels （before vs. after treatment） in the treatment group was higher than that in the control group （P＜0.01）. Compared with the baseline within group， both groups showed decreases in the total score of AFEQT Questionnaire， scores of the daily life dimension， treatment worry dimension， symptom dimension， and TCM syndrome scores at 4 weeks， 8 weeks， and 12 weeks after treatment. Meanwhile， the score of the treatment satisfaction dimension of AFEQT increased in both groups （P＜0.01）， and the improvements in all the above scores in the treatment group were superior to those in the control group at all time points （P＜0.05 or P＜0.01）. All safety indicators of patients in both groups were within the normal range before treatment and at 12 weeks after treatment， and no adverse reactions or adverse events occurred in either group. ConclusionModified Zhigancao Granules can reduce the early recurrence rate following radiofrequency ablation in AF patients with qi-yin deficiency syndrome， improve clinical symptoms and quality of life， suppress inflammatory response， and show good safety.

Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of type Ⅰ collagen(Col1)and type Ⅲ collagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.

Type 2 inflammation（T2 inflammation）is an immune response mediated by Th2 cells，eosinophils，type 2 innate lymphocytes，and other cells. Its pathological characteristics are manifested by the abnormally high expression of type 2 cytokines such as IL-4，IL-5，and IL-13，and it widely involves allergic diseases including asthma，allergic rhinitis，and atopic dermatitis. Ginsenosides are the core active ingredients of ginseng and the key substances for ginseng to exert its pharmacological effects. It has anti-inflammatory and immunomodulatory effects. This article reviews the mechanism of action，experimental research progress，and clinical application prospects of ginsenosides in T2 inflammation，explores the therapeutic potential and clinical challenges of ginsenosides，and proposes future research directions.

Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of type Ⅰ collagen(Col1)and type Ⅲ collagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.

Objective:To observe the occurrence and closure of iatrogenic atrial septal defect (IASD) after left atrial appendage occlusion (LAAo) and atrial fibrillation cryoballoon ablation (CBA), and to identify potential factors that may affect the occurrence of IASD.Methods:A total of 383 patients who underwent successful LAAo surgery in the Department of Cardiology at the Nanjing Hospital Affiliated to Nanjing Medical University from June 7, 2016 to December 2, 2020, and atrial fibrillation CBA surgery from December 29, 2016 to September 10, 2020 were retrospectively selected. Patients were followed up with echocardiography at 1 month, 3 months, 6 months, 1 year, and>1 year after surgery to determine the occurrence of IASD. The incidence of IASD between the two groups was compared, and clinical data between the two groups with and without IASD were analyzed to identify the relevant factors for the occurrence of IASD.Results:One month after CBA surgery for atrial fibrillation [73.8%(138/187) vs 47.9%(67/140), P<0.001], 3 months [39.0%(57/146) vs 13.6%(16/118), P<0.001], 6 months [17.7%(22/124) vs 3.6%(4/110), P=0.001], 1 year [11.8%(15/127) vs 1.8%(2/112), P=0.003], and one year later [9.8%(13/133) vs 0.9%(1/116), P=0.002], the incidence of IASD was significantly higher than those in LAAo. Compared with the non IASD group, the IASD group had a lower proportion of males [59.0%(121/205) vs 83.6%(102/122), P<0.001], and a higher proportion of paroxysmal atrial fibrillation [61.5%(126/205) vs 45.9%(56/122), P=0.006]. Logistic regression analysis found a significant correlation between women and CBA with postoperative IASD. Conclusions:Compared with LAAo, the incidence of IASD after CBA for atrial fibrillation is higher, and some IASD persist for more than 1 year after surgery. Women are significantly associated with IASD.

Finding stable expression sites on the chromosomes of Chinese hamster ovary (CHO) cells is an effective method to solve the problem of unstable expression of CHO cells in long-term culture. Our group used lentiviral transfection to integrate the tracer gene (Zsgreen1) into the chromosome of CHO cells and found multiple potential stable expression sites. This study verified the ability of one of the sites located in the 148052-148157 bp region on chromosome NW_003614241.1 to stably express exogenous proteins.The expression of Zsgreen1 gene was first observed, and CRISPR/Cas9 technology was then used to integrate the enhanced green fluorescent protein (EGFP) gene into this site. Three strains of EGFP gene integrated cells were obtained. After 60 generations of suspension culture, the fluorescence intensity of the cells had no significant changes, which proved that this site can stably express the EGFP gene. The same method was used to construct recombinant CHO cell lines expressing the human serum albumin (HSA) gene, and was verified by Western blot that this site could express and secrete HSA. It shows that the above-mentioned sites can be integrated and can stably express exogenous proteins.

Objective: To explore the relationship between fragmented QRS complex(fQRS) and coronary collateral circulation(CCC) in patients with chronic total occlusion(CTO)lesion without prior myocardial infarction. Methods: This retrospective study analyzed 238 consecutive patients with CTO lesion in one of the major coronary arteries from May 2014 to October 2015 in our department. Patients were divided into poor CCC group (grade 0 and 1, 58 cases) and good CCC group(grade 2 and 3, 180 cases) based on Rentrop′s classification of CCC. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous electrocardiogram leads corresponding to a major coronary artery territory. Multivariate logistic regression was used to analyze the relationship between CCC and fQRS on electrocardiogram. Results: Compared with good CCC group, patients in poor CCC group had older age((65.2±8.9)years old vs. (60.3±10.1) years old, P=0.03), higher plasma glucose ((7.22±3.00) mmol/L vs.(6.31±1.83)mmol/L, P=0.04), and lower left ventricular ejection fraction ((45.2±11.4)% vs. (51.2±13.5)%, P=0.02). None of patients had Rentrop grade 0, the presence of fQRS on ECG in patients with Rentrop grade 1, grade 2, and grade 3 CCC was 69.0% (40/58), 48.6% (35/72) , and 19.4% (21/108), respectively (P<0.01). The presence of fQRS were higher in poor CCC group than in good CCC group (69.0%(40/58)vs. 31.1%(56/180), P<0.01), and number of leads with fQRS were higher in poor CCC group than in good CCC group (3(0, 4)vs.0(0, 3), P<0.01). Multivariate logistic regression analysis demonstrated that poor CCC growth in patients with CTO lesion without prior myocardial infarction was independently related to the presence of fQRS (OR=3.659, 95%CI 1.619-8.217, P<0.01). Conclusion Poor CCC in patients with CTO lesion without prior myocardial infarction is independently related to the presence of fQRS on electrocardiogram.

OBJECTIVETo determine the mid-term effects of cutting balloon angioplasty (CBA) on in-stent restenosis.

METHODSA total of 69 patients with in-stent restenosis were divided into 2 groups randomly: cutting balloon angioplasty and plain old balloon angioplasty. The mechanisms of restenosis and dilation results were determined by quantitative coronary angiography and intravascular ultrasound. Follow-up was performed.

RESULTSThe procedural success rate was 100% without death and acute closure. One patient experienced dissection at the distal end of the stent and needed another stent. The mean follow-up period was 6.7 +/- 2.3 months. The final re-restenosis rate was 15% and 18% at 3 months and 6 months respectively, markedly lower than after plain old balloon angioplasty (38% and 43%). Acute gain by intravascular ultrasound (IVUS) was 1.72 +/- 0.52 mm after cutting balloon angioplasty, higher than 1.15 +/- 0.54 mm after plain old balloon angioplasty. The lumen diameter late loss in the cutting balloon group was 0.26 +/- 0.05 mm and 0.38 +/- 0.06 mm at 3 months and 6 months respectively, significantly lower than for those in conventional balloon group (0.78 +/- 0.19 mm and 0.89 +/- 0.16 mm, respectively, P < 0.001). As shown by IVUS, the main mechanism of cutting balloon angioplasty was marked reduction of plaque area without significant increase of vessel area (less vessel trauma).

CONCLUSIONCutting balloon angioplasty is feasible and effective for the treatment of in-stent restenosis with less vessel trauma.

Aged ; Angioplasty, Balloon ; methods ; Coronary Angiography ; Coronary Restenosis ; therapy ; Coronary Vessels ; pathology ; physiopathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Stents ; Time Factors ; Treatment Outcome

AimTo evaluate the effects of different doses of valsartan on blood pressure and left ventricular hypertrophy in spontaneously hypertensive rats (SHR) . MethodsEighteen SHR(fourteenweek-old, male) were divided into three groups (six rats in each group ): SHR control group in which the rats were fed with normal saline; low dose valsartan group in which the rats were fed with valsartan 8 mg· kg-1 · d-1 and high dose valsartan group in which the rats were fed with valsartan 24 mg · kg -1 · d-1, all for 8 weeks. The rats in the WKY control group(n ＝ 6) were fed with normal saline for 8 weeks. Results SBP, LVM/ BW and TDM of SHR were remarkably lower than those of the control after drug intervention, and the effect on SBP, LVM/ BW and TDM was most remarkable in the high dose valsartan group. ConclusionDifferent doses of valsartan can decrease SBP of SHR and inhibit the progression of ventricular hypertrophy.