[Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on Angâ ¡-induced cardiomyocyte hypertrophy].

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.

[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

[Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure].

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Expression of PCT, BNP and Inflammatory Factors in Children with Kawasaki Disease and Their Correlation with Coronary Artery Lesions.

Background: Kawasaki disease (KD), as one of the most common vascular diseases in children, will cause the risk of coronary artery lesions (CAL) without treatment. This study is to explore the expression of procalcitonin (PCT), brain natriuretic peptide (BNP), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin-6 (IL-6) in children with KD and their correlation with CAL. Methods: 86 KD children in Baoding Hospital of Beijing Children's Hospital were selected as the study subjects from January 2020 to June 2021. According to whether CAL occurred, they were divided into the CAL group (n=30) and NCAL group (n=56). The clinical data of the two groups were collected from the medical record system. The levels of PCT and BNP were detected by chemiluminescence microparticle assay, the CRP level was detected by immunoturbidimetry, and the levels of TNF-α and IL-6 were detected by flow immunofluorescence method. The relationship of PCT, BNP, and inflammatory factors with CAL in KD children was explored by Pearson correlation analysis. Results: The comparative result of clinical data showed no overt difference in gender, disease types, age and blood routine indexes between the two groups, except for coronary artery diameter (P >.05). The levels of PCT, BNP, CRP, TNF-α and IL-6 in CAL group were (1.70±0.39) µg/L, (289.21±29.78) ng/L, (83.16±17.35) mg/L, (9.38±1.23) pg/mL and (59.97±0.97) ng/mL, respectively. The levels of PCT, BNP, CRP, TNF-α and IL-6 in NCAL group were (1.04±0.18) µg/L, (170.85±23.58) ng/L, (69.70±16.64) mg/L, (6.32±0.73) pg/mL and (44.16±11.97) ng/mL, respectively. The levels of each index in the CAL group were notably higher than in the NCAL group (P < .001). Pearson correlation analysis revealed that PCT, BNP, CRP, TNF-α and IL-6 were positively correlated with CAL in KD children (r=0.829, 0.865, 0.823, 0.894, 0.784, P < .001). Conclusion: The increase of PCT, BNP, and inflammatory factors has a certain warning effect on CAL in KD children. In clinical practice, health care professionals should strengthen the detection of PCT, BNP and inflammatory factors in KD children, carry out early monitoring of CAL in children with high expression of biomarkers, and formulate personalized preventive intervention based on the disease progress, so as to reduce the risk of cardiovascular disease. However, due to the limitations of research conditions and methods, the sample size of this study is small, which may affect the reliability and representativeness of the conclusion. In order to provide a new direction for the clinical prevention and treatment of the disease, future work will improve the research design, expand the sample size, and carry out more in-depth exploration on the prediction of CAL in KD children.

[Clinical effect of Shenfu injection combined with glucocorticoid on patients with acute left heart failure complicated with bronchospasm].

OBJECTIVE: To investigate the clinical effect of Shenfu injection combined with glucocorticoid in the treatment of acute left heart failure complicated with bronchospasm. METHODS: A prospective study was conducted.Ninety patients with acute left heart failure complicated with bronchospasm admitted to Huai'an Second People's Hospital from January 2021 to July 2022 were selected and divided into conventional treatment group, hormone therapy group and combined treatment group according to random number table method, with 30 cases in each group. All patients in the 3 groups received basic Western medicine treatment. On this basis, the conventional treatment group was given 0.25-0.50 g aminophylline injection plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 100 mL slow intravenous infusion, 1-2 times a day. In the hormone treatment group, 1 mg of budesonide suspension for inhalation was diluted to 2 mL by 0.9% sodium chloride injection, twice a day, and applied until 48 hours after the pulmonary wheezing disappeared. The combined treatment group was given glucocorticoid combined with Shenfu injection 80 mL plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 250 mL intravenously, once a day. All treated for 1 week. The general data, traditional Chinese medicine (TCM) syndrome score, TCM syndrone efficacy index, acute left heart failure efficacy, bronchospasm efficacy, systolic blood pressure (SBP), mean arterial pressure (MAP), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and safety of the 3 groups were compared. The patients were followed up for 6 months, and the mortality and re-hospitalization rate of the 3 groups were recorded. RESULTS: Among the 90 patients, a total of 83 patients completed the study, excluding the cases dropped due to death and other reasons. There were 29 cases in the combined treatment group, 25 cases in the hormone therapy group and 29 cases in the conventional treatment group. There were no significant differences in age, gender, course of disease, and previous history (history of diabetes, history of hypertension, history of hyperlipidemia) among the 3 groups. Therefore, they were comparable. The difference of TCM syndrome score before and after treatment, TCM syndrome efficacy index of combined treatment group and hormone therapy group were higher than those of conventional treatment group [difference of TCM syndrome score: 15.14±5.74, 13.24±5.75 vs. 10.62±5.87, TCM syndrome efficacy index: (67.84±14.31)%, (59.94±14.26)% vs. (48.92±16.74)%, all P < 0.05], and the difference of TCM syndrome score and TCM syndrome efficacy index of combined treatment group were higher than those of hormone treatment group (both P < 0.05). The total effective rate of acute left heart failure and bronchospasm in the combined treatment group was significantly higher than that in the conventional treatment group (total effective rate of acute left heart failure: 96.55% vs. 75.86%, total effective rate of bronchospasm: 93.10% vs. 65.52%, both P < 0.05). The difference of serum NT-proBNP before and after treatment in combination therapy group and hormone therapy group was significantly higher than that in conventional treatment group (ng/L: 7 922.86±5 220.31, 7 314.92±4 450.28 vs. 4 644.79±3 388.23, all P < 0.05), and the difference of serum NT-proBNP before and after treatment in the combined treatment group was significantly higher than that in the hormone treatment group (P < 0.05). There were no significant differences in SBP difference, MAP difference, mortality and re-hospitalization rate among the 3 groups. No adverse reactions occurred in the 3 groups during treatment. CONCLUSIONS: Shenfu injection combined with glucocorticoid is effective in the treatment of patients with acute left heart failure complicated with bronchospasm. It is superior to glucocorticoid and aminophylline in relieving bronchospasm, reducing NT-proBNP level and improving total effective rate, and has good prognosis and safety.

Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China.

OBJECTIVE: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited. METHODS: The relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves. RESULTS: We found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592-0.631), sensitivity of 50.7%, and specificity of 68.0%. CONCLUSION: An increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states. Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).

Diagnostic Value of cTnl, NT-pro BNP, and Combined Tests in Acute Myocardial Infarction Patients.

Objective: Acute myocardial infarction (AMI) is characterized by heart damage resulting from blocked blood flow. Prompt diagnosis is vital for timely treatment and saving lives. This study aimed to evaluate the diagnostic value of cTnl, NT-pro BNP, and a combined test in AMI patients. Methods: In this study, a retrospective observational design was employed, and we selected 221 patients with AMI admitted to our hospital within a 3-year period as the research subjects and included them in the AMI group. Additionally, 200 patients from the control group, who visited our hospital for physical examinations, were selected to compare the expressions of cardiac Troponin I (cTnl) and N-Terminal pro-B-type Natriuretic Peptide (NT-pro BNP) between the two groups. Receiver Operating Characteristic (ROC) curves were constructed to analyze the diagnostic value of cTnl combined with NT-pro BNP for AMI. Furthermore, AMI patients were categorized into four groups based on the New York Heart Association (NYHA) classification (grades I, II, III, and IV). The differences in cTnl, NT-pro BNP, and Left Ventricular Ejection Fraction (LVEF) were compared among the AMI patients with different cardiac function grades to analyze their correlation and diagnostic value in assessing the severity of AMI-related cardiac insufficiency. Results: The levels of cTnl and NT-pro BNP in AMI patients were significantly higher than those in the control group, and their combined detection effectively facilitated the diagnosis of AMI occurrence. Moreover, cTnl and NT-pro BNP concentrations increased with the severity of cardiac dysfunction (NYHA grades) and showed a notable negative correlation with LVEF. Furthermore, the combined testing of cTnl and NT-pro BNP demonstrated significant value in evaluating the severity of AMI in patients. Conclusions: The combined detection of cTnl and NT-pro BNP holds considerable application value in diagnosing AMI occurrence and assessing its severity.

Effect of Levosimendan on B-type Natriuretic Peptide Levels in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aims to evaluate the effects of levosimendan on B-type natriuretic peptide (BNP) levels in patients with decompensated heart failure and assess the efficacy and safety of levosimendan in treating left heart failure. Methods: Randomized controlled trials (RCTs) were identified through searches in the Chinese Biomedical Literature Database (CBM), Chinese Academic Journal Full Text Database (CNKI), Wanfang Database (CECDB), VIP Chinese Scientific, PubMed, Cochrane Library, and Web of Science. Quality assessment and data extraction were performed for the included studies, and meta-analysis was conducted using Review Manager 5.2 software. Results: The meta-analysis revealed a statistically significant difference in the regulatory effect of levosimendan on BNP levels in patients with stage III heart failure compared to the control group [OR = 2.12, 95% CI (1.22, 3.67), P = .008, I2 = 37%, Z = 2.67]. Additionally, leosimendan showed a significant effect on BNP levels in patients with stage IV heart failure [OR = 1.88, 95% CI (1.27, 2.79), P = .002, I2 = 0%, Z = 3.14], compensatory heart failure [OR=2.97, 95% CI (1.81, 4.86), P < .0001, I2 = 55%, Z = 4.32], and decompensated heart failure [OR = 1.98, 95% CI (1.59, 2.47), P < .00001, I2 = 76%, Z = 6.07]. Conclusions: Levosimendan administration demonstrated improved cardiac function and a significant reduction in plasma BNP levels in patients with decompensated heart failure.

Astragaloside IV for Heart Failure: Preclinical Evidence and Possible Mechanisms, A Systematic Review and Meta-Analysis.

OBJECTIVE: To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF). METHODS: PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0. RESULTS: Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model). CONCLUSIONS: AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.

[Clinical observation of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in patients with acute heart failure].

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.

The Pulse of It: Dietary Inclusion of Up to 45% Whole Pulse Ingredients with Chicken Meal and Pea Starch in a Complete and Balanced Diet Does Not Affect Cardiac Function, Fasted Sulfur Amino Acid Status, or Other Gross Measures of Health in Adult Dogs.

BACKGROUND: Pulses are an attractive alternative protein source for all mammals; however, recent reports suggest that these ingredients may be related to developing dilated cardiomyopathy in dogs. OBJECTIVES: The primary objective of this study was to quantify the effects of dietary pulse intake by adult dogs on cardiac function using echocardiographic measurements and cardiac biomarkers N-terminal pro-B-type natriuretic peptide and cardiac troponin I (cTnI). Second, to investigate the effects of pulse consumption on plasma sulfur amino acid (SAA) concentrations as pulses are generally low in SAA and may limit taurine synthesis. Last, to assess the general safety and efficacy of feeding pulse-containing diets on canine body composition and hematological and biochemical indices. METHODS: Twenty-eight privately-owned domestic Siberian Huskies (13 females; 4 intact, and 15 males; 6 intact) with a mean age of 5.3 ± 2.8 y (± SD) were randomly assigned to 1 of 4 dietary treatments (n = 7/treatment), with equal micronutrient supplementation and increasing whole pulse ingredient inclusion (0%, 15%, 30%, and 45%) with pea starch used to balance protein and energy. RESULTS: After 20 wks of feeding, there were no differences (P > 0.05) in echocardiographic parameters, N-terminal pro-B-type natriuretic peptide, and cTnI concentrations among treatments or across time within treatment (P > 0.05), indicating no differences in cardiac function among treatments. Concentrations of cTnI remained below the safe upper limit of 0.2 ng/mL for all dogs. Plasma SAA status, body composition, and hematological and biochemical indices were similar among treatments and over time (P > 0.05). CONCLUSIONS: The results from this study suggest that increasing the inclusion of pulses up to 45% with the removal of grains and equal micronutrient supplementation does not impact cardiac function concurrent with dilated cardiomyopathy, body composition, or SAA status and is safe for healthy adult dogs to consume when fed for 20 wks.

Efficacy and safety evaluation of Shenmai injections for dilated cardiomyopathy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Shenmai Injection (SMI), a Chinese herbal injection, is widely used in China for the adjuvant treatment of patients with dilated cardiomyopathy (DCM), yet its clinical efficacy and safety remain controversial. PURPOSE: The aim of this study was to systematically evaluate the efficacy and safety of SMI in the treatment of DCM. METHODS: Randomised controlled trials (RCTs) of SMI in the treatment of DCM were searched for and collected from the PubMed, EMBASE, Cochrane Library, SinoMed, Wan Fang, CNKI, and VIP databases between the dates of establishment of each database and July 1, 2022. The methodological quality of the included studies was assessed, while the risk of bias was based on the Cochrane Collaboration tool. All data were analysed using the R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS: In total, 16 RCTs, including 1,455 participants, were examined in this study. Evidence showed that the combination of SMI treatment and conventional treatment appears to significantly increase the clinical efficacy rate (OR=3.65, 95%CI (2.52, 5.28), p < 0.01), improve cardiac function (e.g. increase left ventricular ejection fraction (LVEF) (MD=5.31, 95%CI (4.21, 6.40), p < 0.01), decrease left ventricular end-diastolic dimension (LVEDD) (MD=-4.57, 95% CI (-7.10, -2.04); p < 0.01) and left ventricular end-systolic diameter (LVESD) (MD=-2.46, 95% CI (-3.60, -1.33); p < 0.01), decrease brain natriuretic peptide (BNP) (MD=-215.85, 95% CI (-241.61, -190.10); p < 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (MD=-504.42, 95% CI (-687.73, -321.10); p < 0.01), and increase 6-min walk distance (6MWD) (MD=114.08, 95% CI (42.32, 185.85); p < 0.01).In addition, no serious adverse effects associated with SMI were observed during the study period, thus suggesting that SMI is safe. However, the quality of evidence for these results was rated as "very low" to "low", mainly due to the poor methodological quality of the included RCTs, the small sample size, the high heterogeneity, and potential publication bias. CONCLUSION: In the present work, we provide evidence that combined SMI therapy is beneficial and safe for improving cardiac function in patients with DCM. However, due to limitations posed by the low methodological quality of the included trials, more rigorous and high-quality RCTs are needed to provide solid evidence.

Clinical observation of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in patients with acute heart failure / 中华内科杂志

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.

[Network Meta-analysis of 11 Chinese patent medicines in treatment of dilated cardiomyopathy].

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.

Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress.

Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS. Methods: Eighty male SD rats were randomly divided into two groups: controls (n = 20) and diabetes (n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 µg/kg/d), and high-dose relaxin-3 group (2 µg/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1α, and tumor necrosis factor (TNF)-α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis. Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls (P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group (P < 0.05). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls (P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks (P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls (P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression. Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.

Effects and Safety of Oral Iron for Heart Failure with Iron Deficiency: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Background: Oral iron supplement is commonly prescribed to heart failure patients with iron deficiency. However, the effects of oral iron for heart failure remain controversial. This study included randomized controlled trials (RCTs) for meta-analysis to evaluate the effects of oral iron for heart failure patients. Methods: Nine databases (The Cochrane Library, Embase, PubMed, CINAHL, Web of science, CNKI, SinoMed, VIP, and Wanfang) were searched for RCTs of oral iron for heart failure from inception to October 2021. The effects were assessed with a meta-analysis using Revman 5.3 software. The trial sequential analysis was performed by TSA 0.9.5.10 beta software. The risk of bias of trials was evaluated via Risk of Bias tool. The evidence quality was assessed through GRADE tool. Results: Four studies including 582 patients with heart failure and iron deficiency were enrolled. The results indicated that oral iron treatment could improve left ventricular ejection fraction (LVEF, MD = 1.52%, 95% CI: 0.69 to 2.36, P = 0.0003) and serum ferritin (MD = 1.64, 95% CI: 0.26 to 3.02, P = 0.02). However, there was no between-group difference in the 6-minute walk distances (6MWT), N terminal pro B type natriuretic peptide (NT-proBNP) or hemoglobin level when compared with control group. Subgroup analyses revealed that the effects of oral iron on 6 MWT and serum ferritin could not be affected by duration and frequency of oral iron uptakes. In trial sequential analysis of LVEF and serum ferritin, the Z-curves crossed the traditional boundary and trail sequential monitoring boundary but did not reach the required information size. Conclusion: This analysis showed that oral iron could improve cardiac function measured by LVEF, and iron stores measured serum ferritin, but lack of effect on exercise capacity measured by 6 MWT, and iron stores measured by hemoglobin. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.

The efficacy of Yiqi Huoxue therapy for chronic heart failure: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF. METHODS: Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale. RESULTS: Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15-1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17-1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05-3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60-1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23-1.56), and in lowering down the TCM syndrome scores (SMD = -0.78, 95% CI -0.91 to -0.64), Minnesota Living with Heart Failure questionnaire (SMD = -1.01, 95% CI -1.56 to -0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28-0.89), B-type natriuretic peptide (SMD = -0.89, 95% CI -1.52 to -0.25), NT-proBNP (SMD = -2.07, 95% CI -3.34 to -0.08), and C-reactive protein (SMD = -2.04, 95% CI -4.12 to -0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E' between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were "low" and "very low" according to the GRADE assessment. CONCLUSION: YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.

Baroreflex activation therapy with the Barostim™ device in patients with heart failure with reduced ejection fraction: a patient level meta-analysis of randomized controlled trials.

AIMS: Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho-vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline-recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFrEF. METHODS AND RESULTS: An individual patient data (IPD) meta-analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline-directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6-month changes in 6-min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT-proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of -13 points (95% CI -17, -10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT-proBNP <1600 pg/ml, regardless of the cardiac resynchronization therapy indication status. CONCLUSION: An IPD meta-analysis suggests that BAT improves exercise capacity, NYHA class, and QoL in HFrEF patients receiving GDMT. These clinically meaningful improvements were consistent across the range of patients studies. BAT was also associated with an improvement in NT-proBNP in subjects with a lower baseline NT-proBNP.

Serum Cat S, TSP-1, IL-11, BNP and sST2 Diagnostic and Prognostic Value in Chronic Heart Failure.

Context: Objectives • This study aimed to assess the diagnostic value of serum brain natriuretic peptide (BNP), cathepsin S (Cat S), serum soluble ST2 receptor (sST2), platelet reactive protein-1 (TSP-1) and interleukin-11 (IL-11) in patients with chronic heart failure (CHF). Context: Materials and Methods • A total of 112 patients admitted to in our hospital with HF were enrolled as the HF group and 120 healthy people undergoing physical examination were assigned to the control group. The serum levels of Cat S, TSP-1, IL-11, sST2 and BNP were measured and compared in the subgroups categorized according to New York Heart Association (NYHA) Functional Classification. Pearson correlation was applied to analyze the correlation between serum Cat S, TSP-1, IL-11, sST2 and BNP and NYHA functional class. Moreover, multivariate logistic regression was used to analyze the HF influencing factors. Context: Results • No correlation was found between the 2 groups in terms of general information, such as age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, smoking and heart rate (P > .05). The left ventricular ejection fraction (LVEF) in the HF group was lower than in the control group, while the level of LV end diastolic dimension (LVEDD) and left ventricular end diastolic volume (LVEDV) was significantly higher (P < .05). The levels of Cat S, TSP-1, sST2, IL-11 and BNP in the HF group were higher than in the control group (P < .05). The levels of Cat S, TSP-1, sST2, IL-11 and BNP in the grade IV group were higher than those in the grade II and III groups (P < .05). Serum Cat S, TSP-1, IL-11, sST2 and BNP levels were positively correlated with NYHA functional class (R = 0.568, 0.409, 0.472, 0.547, 0.632, respectively) (P < .001). Multivariate logistic regression analysis demonstrated that LVEF, LVEDD, LVEDV, Cat S, TSP-1, IL-11, sST2 and BNP were independent markers of CHF. Context: Conclusion • Abnormal Cat S, TSP-1, IL-11, sST2 and BNP levels were found in patients with CHF, and were highly associated with the cardiac function grades of CHF. Therefore, serum Cat S, TSP-1, IL-11, sST2 and BNP levels can serve as independent markers for CHF.

Melatonin supplementation improves N-terminal pro-B-type natriuretic peptide levels and quality of life in patients with heart failure with reduced ejection fraction: Results from MeHR trial, a randomized clinical trial.

BACKGROUND: Melatonin, the major secretion of the pineal gland, has beneficial effects on the cardiovascular system and might advantage heart failure with reduced ejection fraction (HFrEF) by attenuating the effects of the renin-angiotensin-aldosterone and sympathetic system on the heart besides its antioxidant and anti-inflammatory effects. HYPOTHESIS: We hypothesized that oral melatonin might improve echocardiographic parameters, serum biomarkers, and a composite clinical outcome (including quality of life, hospitalization, and mortality) in patients with HFrEF. METHODS: A placebo-controlled double-blinded randomized clinical trial was conducted on patients with stable HFrEF. The intervention was 10 mg melatonin or placebo tablets administered every night for 24 weeks. Echocardiography and measurements of N-terminal pro-B-type natriuretic peptide (NT-Pro BNP), high-sensitivity C-reactive protein, lipid profile, and psychological parameters were done at baseline and after 24 weeks. RESULTS: Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT-Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2-215.7], p = .044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18-1.69], p = .017), quality of life (5.8 [0.9-12.5], p = .037), and New York Heart Association class (odds ratio: 12.9 [1.6-102.4]; p = .015) at the end of the trial. Other studied outcomes were not significantly different between groups. CONCLUSIONS: Oral melatonin decreased NT-Pro BNP and improved the quality of life in patients with HFrEF. Thus it might be a beneficial supplement in HFrEF.