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.

OBJECTIVES: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway. METHODS: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for the blank control group, post-myocardial infarction heart failure was induced by coronary constriction. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method. Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting. RESULTS: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins decreased (all P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction. CONCLUSIONS Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Myocardial Infarction/complications* ; Transforming Growth Factor beta1/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Heart Failure/pathology* ; Myocardium/metabolism* ; Fibrosis ; Amino Acid Oxidoreductases/metabolism* ; Interleukin-11/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Matrix Metalloproteinase 9/metabolism*

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.

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 excavate the TCM syndrome of chronic heart failure from 1973 to 2023 and summarize the evolution of the characteristics of medical syndrome.Methods The relevant literature on clinical research on TCM syndromes in three databases including CNKI from January 1,1973 to October 1,2023 was searched,and SPSS 21.0 and Rstudio software were used to conduct descriptive statistical analysis,association rule analysis,and cluster analysis on the distribution characteristics of TCM syndrome types and pattern elements in the final literature.Results A total of 218 literatures,including 41604 patients,covering 29 provinces,municipalities and autonomous regions across the country,were included,of which 179 articles explicitly reported the TCM composite syndrome type,including 31123 patients.A total of 71996 pattern elements were extracted,and the common elements included qi deficiency,blood stasis,phlegm turbidity,etc.The main location of the disease include heart,liver,spleen,etc.The characteristics of TCM syndromes in different regions and different periods show certain evolution rules,from 1973 to 2023,the proportion of qi deficiency and blood stasis pattern and phlegm and stasis mutual obstruction pattern showed an upward trend.The proportion of simple false evidence increased from 1994 to 2003 compared with 1973 to 1993,but decreased from 2004 to 2023,and was lower than that from 1973 to 1993.The proportion of yang deficiency water pan syndrome showed a downward trend;The evolution of syndromes in different regions has changed from deficiency to deficiency and real mixed syndrome,for example,North China,which has the highest proportion,has changed from cardiopulmonary qi deficiency to qi deficiency and blood stasis.In recent years,the proportion of heart,liver and spleen in the chronic heart failure syndrome pattern showed an overall upward trend,the proportion of the syndrome elements of the deficiency syndrome showed a downward trend,and the proportion of the syndrome elements of the standard disease syndrome showed an upward trend.Conclusion The characteristics of chronic heart failure syndrome are always the evidence of deficiency and reality,with"deficiency and qi retention"as the core pathogenesis,and the main disease sites are the heart,liver,and spleen,and the pattern elements composed of qi deficiency,phlegm turbidity,blood stasis,and water drinking gradually occupy a dominant position,and the TCM pattern type of chronic heart failure may show a trend of"deficiency of phlegm and stasis"in the future.

Objective To excavate the TCM syndrome of chronic heart failure from 1973 to 2023 and summarize the evolution of the characteristics of medical syndrome.Methods The relevant literature on clinical research on TCM syndromes in three databases including CNKI from January 1,1973 to October 1,2023 was searched,and SPSS 21.0 and Rstudio software were used to conduct descriptive statistical analysis,association rule analysis,and cluster analysis on the distribution characteristics of TCM syndrome types and pattern elements in the final literature.Results A total of 218 literatures,including 41604 patients,covering 29 provinces,municipalities and autonomous regions across the country,were included,of which 179 articles explicitly reported the TCM composite syndrome type,including 31123 patients.A total of 71996 pattern elements were extracted,and the common elements included qi deficiency,blood stasis,phlegm turbidity,etc.The main location of the disease include heart,liver,spleen,etc.The characteristics of TCM syndromes in different regions and different periods show certain evolution rules,from 1973 to 2023,the proportion of qi deficiency and blood stasis pattern and phlegm and stasis mutual obstruction pattern showed an upward trend.The proportion of simple false evidence increased from 1994 to 2003 compared with 1973 to 1993,but decreased from 2004 to 2023,and was lower than that from 1973 to 1993.The proportion of yang deficiency water pan syndrome showed a downward trend;The evolution of syndromes in different regions has changed from deficiency to deficiency and real mixed syndrome,for example,North China,which has the highest proportion,has changed from cardiopulmonary qi deficiency to qi deficiency and blood stasis.In recent years,the proportion of heart,liver and spleen in the chronic heart failure syndrome pattern showed an overall upward trend,the proportion of the syndrome elements of the deficiency syndrome showed a downward trend,and the proportion of the syndrome elements of the standard disease syndrome showed an upward trend.Conclusion The characteristics of chronic heart failure syndrome are always the evidence of deficiency and reality,with"deficiency and qi retention"as the core pathogenesis,and the main disease sites are the heart,liver,and spleen,and the pattern elements composed of qi deficiency,phlegm turbidity,blood stasis,and water drinking gradually occupy a dominant position,and the TCM pattern type of chronic heart failure may show a trend of"deficiency of phlegm and stasis"in the future.

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 systematically evaluate the efficacy and safety of Compound Danshen Dripping Pills combined with conventional western medicine in the treatment of coronary heart disease complicated with diabetes mellitus.Methods Wanfang database,CNKI,VIP,SinoMed,Cochrane Library,PubMed,Embase and Web of Science databases were searched to collect randomized controlled trials(RCTs)of Compound Danshen dripping pills combined with conventional western medicine in the treatment of coronary heart disease complicated with diabetes mellitus.The retrieval time is from the establishment of the database to May 2023.Two researchers independently completed literature screening,data collation and risk of bias evaluation.RevMan 5.4 software was used for Meta-analysis.Results Twenty-four RCTs with a total of 2 546 patients were included.Meta-analysis showed that the treatment of Compound Danshen Dripping Pills combined with conventional western medicine was better than that of conventional western medicine in improving the total effective rate of coronary heart disease complicated with diabetes mellitus[OR=4.93,95%CI(3.49,6.98),P＜0.000 01],plasma adiponectin[MD= 2.79,95%CI(2.30,3.27),P＜0.000 01],reducing fasting blood glucose[SMD=-1.06,95%CI(-1.24,-0.88),P＜0.000 01],postprandial two-hour blood glucose[MD=-1.53,95%CI(-1.71,-1.35),P＜0.000 01],glycosylated hemoglobin[MD=-1.56,95%CI(-2.01,-1.11),P＜0.000 01],homocysteine[MD=-8.47,95%CI(-8.89,-7.97),P＜0.000 01],low density lipoprotein[MD=-0.46,95%CI(-0.69,-0.24),P＜0.000 01],total cholesterol[MD=-0.45,95%CI(-1.11,-0.20),P=0.005],triglycerides[MD=-0.42,95%CI(-0.50,-0.34),P＜0.000 01],interleukin 6[SMD=-1.34,95%CI(-1.61,-1.07),P＜0.000 01],cardiovascular adverse events[OR=0.35,95%CI(0.19,0.64),P=0.000 6],incidence of adverse reactions[OR=0.45,95%CI(0.24,0.86),P=0.01].Conclusion Compound Danshen Dripping Pills combined with conventional western medicine in the treatment of coronary heart disease with diabetes mellitus is more effective than conventional western medicine treatment,and with better safety.However,due to the limit of the quality of the included studies and other factors,the above conclusions still need to be verified by more high-quality clinical trials.

Objective To investigate the levels of pro-inflammatory cytokine interferon (IFN)-γand anti-inflammatory cytokine interlenkin (IL)-10 in expressed prostatic secretions (EPS) of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and their clinical significance. Methods The levels of IFN-γ and IL-10 in EPS of 20 patients with CP (type Ⅲ A, group A ), 20 patients with CPPS (type Ⅲ B,group B) and 10 healthy men (control group) were measured using enzyme-linked immunosorbent assay (ELISA). The results were analyzed comparatively with NIH-chronic prostatitis symptom index (NIH-CPSI).Results The levels of IFN-γ in EPS of group A and group B were ( 14.92 ± 7.85 ), ( 13.74 ± 5.96) ng/L respectively, which were higher than that in control group [(7.47 ± 1.40) ng/L] (P ＜ 0.05 ). And the levels of IL-10 in EPS of group A and group B were (216.40 ± 33.65 ), (223.70 ± 45.21 ) ng/L respectively, which were higher than that in control group [( 162.10 ± 43.81 ) ng/L] ( P ＜ 0.05 ). There was no statistically significant difference between group A and group B. No correlation between NIH-CPSI and IFN- γ,IL-10 levels in EPS(P ＞ 0.05 ). Conclusion IFN-γ and IL-10 have a very important role in etiology of CP/CPPS and they can be the objective parameters in the diagnosis of CP/CPPS.

Objective To compare the effect of using ambroxol hydrochloride combined with co-xuanju capsule,co-xuanju capsule and ambroxol hydroehloride in the treatment of semen liquefaction.Methods Sixty semen liquefaction patients were divided randomly into three groups.Clinical trials involving 20 who received ambroxol hydrochloride+co-xuanju capsule(group A),20 co-xuanju capsule(group B) and 20 ambroxol hydrochloride(group C),were carried out for 3 months.The changes of semen liquefaction time and semen quality were measured and assayed before and after treatment Results Compared withpretherapy,various parameters in the semen quality and semen liquefaction time after treatment all had a significantly difference in every group,and the patients of semen liquefaction time less than 60 minutes were 17 in group A,11 in group B and 14 in group C respectively.The results of semen liquefaction time andsemen quality in group A were significandy higher than the other groups(P<0.05),but the results between group B and group C had no significant difference.Conclusion The combination of ambroxol hydrochlorideand co-xuanju capsule can eridently improve the semen liquefaction time and semen quality and is an effective method in treating male infertility.