This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Dalbergia ; Myocardial Ischemia ; Metabolomics ; Heart ; Heart Injuries ; Creatine Kinase, MB Form

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1β(IL-1β) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1β and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1β and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/drug therapy* ; bcl-2-Associated X Protein/metabolism* ; Rats, Sprague-Dawley ; Caspase 3/metabolism* ; Interleukin-18 ; Wolfiporia ; Signal Transduction ; Myocardial Infarction/drug therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Creatine Kinase, MB Form ; Apoptosis ; Polysaccharides/pharmacology* ; Superoxide Dismutase/metabolism* ; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives*

OBJECTIVE: To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice. METHODS: The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury. RESULTS: A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest. CONCLUSIONS The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.
Humans ; Prognosis ; Retrospective Studies ; Interleukin-6 ; ROC Curve ; Sepsis/diagnosis* ; Heat Stroke/complications* ; Risk Factors ; Alanine Transaminase ; Creatine Kinase, MB Form ; Lactic Acid ; Creatine Kinase

Objective: To explore the application value of bispectral index(BIS) , specific protein 100β(S100β) combined with Copeptinin patients with acute severe carbon monoxide poisoning (ASCMP). Methods: A total of 256 patients with acute carbon monoxide poisoning admitted to Hengshui People's Hospital from June 2018 to June 2020 were collected, and they were divided into 30 mild cases, 40 moderate cases and 186 severe cases according to the degree of poisoning. Among them, patients with severe carbon monoxide poisoning were divided into a poor prognosis group (20 cases) and a good prognosis group (166 cases) according to whether adverse events occurred. The changes of creatine kinase isoenzyme (CK-MB) , N-terminal precursor B-type brain natriuretic peptide (NT-proBNP) , BIS, S100β, and Copeptin in poisoned patients were measured. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the significance of relevant indicators for ASCMP patients. Results: Compared with the mild-to-moderate group, CK-MB, NT-proBNP, S100β, Copeptin increased, and BIS value decreased in the severe group (P< 0.05). 24 hours after admission, compared with the good prognosis group, CK-MB, NT-proBNP, S100β, Copeptin in the poor prognosis group increased, and the BIS value decreased (P<0.05). In the poor prognosis group, CK-MB, NT-proBNP, S100β, and Copeptin at 72 hours after admission were all lower than those at 24 hours after admission, and the BIS value was higher than that at 24 hours after admission (P<0.05). Logistic regression analysis showed that ASCMP patients with increased S100β, Copeptin, and decreased BIS values had an increased risk of adverse events (P<0.05). The ROC curve showed that the area under the curve of the combined detection of BIS, S100β and Copeptin was 0.859, which had a great predictive value for the prognosis of ASCMP patients. Conclusion: BIS, S100β combined with Copeptin detection is of great value for early assessment of ASCMP disease and prognosis prediction.
Biomarkers ; Carbon Monoxide Poisoning ; Creatine Kinase, MB Form ; Humans ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; ROC Curve ; S100 Calcium Binding Protein beta Subunit

BACKGROUND: The early identification of heart failure (HF) risk may favorably affect outcomes, and the combination of multiple biomarkers may provide a more comprehensive and valuable means for improving the risk of stratification. This study was conducted to assess the importance of individual cardiac biomarkers creatine kinase MB isoenzyme (CK-MB), B-type natriuretic peptide (BNP), galectin-3 (Gal-3) and soluble suppression of tumorigenicity-2 (sST2) for HF diagnosis, and the predictive performance of the combination of these four biomarkers was analyzed using random forest algorithms. METHODS: A total of 193 participants (80 patients with HF and 113 age- and gender-matched healthy controls) were included from June 2017 to December 2017. The correlation and regression analysis were conducted between cardiac biomarkers and echocardiographic parameters. The accuracy and importance of these predictor variables were assessed using random forest algorithms. RESULTS: Patients with HF exhibited significantly higher levels of CK-MB, BNP, Gal-3, and sST2. BNP exhibited a good independent predictive capacity for HF (AUC 0.956). However, CK-MB, sST2, and Gal-3 exhibited a modest diagnostic performance for HF, with an AUC of 0.709, 0.711, and 0.777, respectively. BNP was the most important variable, with a remarkably higher mean decrease accuracy and Gini. Furthermore, there was a general increase in predictive performance using the multi-marker model, and the sensitivity, specificity was 91.5% and 96.7%, respectively. CONCLUSION The random forest algorithm provides a robust method to assess the accuracy and importance of predictor variables. The combination of CK-MB, BNP, Gal-3, and sST2 achieves improvement in prediction accuracy for HF.
Adult ; Algorithms ; Biomarkers ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Echocardiography ; Female ; Galectin 3 ; blood ; metabolism ; Heart Failure ; blood ; metabolism ; pathology ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; metabolism

Animals ; Cardiovascular Diseases ; drug therapy ; etiology ; Creatine Kinase, MB Form ; blood ; Heart ; drug effects ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Lycium ; chemistry ; Male ; Nitrates ; blood ; Oxidative Stress ; drug effects ; Physical Conditioning, Animal ; adverse effects ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; blood

OBJECTIVE: To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice. METHODS: Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot. RESULTS: Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA. CONCLUSIONS The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.
Animals ; Apoptosis ; Caspase 12 ; Caspase 3 ; metabolism ; Creatine Kinase, MB Form ; blood ; Endoplasmic Reticulum Stress ; Heart Injuries ; physiopathology ; Heat-Shock Proteins ; metabolism ; L-Lactate Dehydrogenase ; blood ; Lung ; pathology ; MAP Kinase Kinase 4 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myocardium ; pathology ; Random Allocation ; Reperfusion Injury ; Transcription Factor CHOP ; metabolism

To investigate the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. HPLC fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were established, and the values of creatinekinase-MB (CK-MB), myoglobin (MYO) and cardiac troponin-T (cTNT) in 3 dose groups (2.25, 13.5, 27.0 g·kg⁻¹, equivalent to the crude herb g·kg⁻¹) of Trichosanthis Fructus and Trichosanthis Fructus strip pieces with myocardial ischemia-reperfusion injury in rats were measured, and the grey relational analysis was used to study the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. With the dosage increase from 2.25 g·kg⁻¹ to 27.0 g·kg⁻¹, the correlation degree of spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces was also enhanced, but the change trend was different between these two groups. According to the frequency of the top 10 peaks in the correlation degree, peak 17, 14, 16, 19, 32, 12, 26, 30, 4, 6 and 2 were the basic effective substances group of Trichosanthis Fructus, peak 6,14,12,32,30,4 and 6 were the basic effective substances group of Trichosanthis Fructus strip pieces. Peak 6, 14, 12, 32, 30, 4 and 26 in fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were the main common pharmacodynamic substance base, among them, peak 6 was 5-hydroxymethyl furfural, peak 14 was vanillic acid and the peak 28 was rutin, but the correlation degree with the efficacy was different. The effect of Trichosanthis Fructus and Trichosanthis Fructus strip pieces on rat myocardial ischemia-reperfusion injury was due to the synergistic effect of the effective substance groups related to the dosage. The essential pharmacodynamic substance groups of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were different, but they shared a common active ingredient group.
Animals ; Chromatography, High Pressure Liquid ; Creatine Kinase, MB Form ; blood ; Cucurbitaceae ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Fruit ; chemistry ; Myocardial Reperfusion Injury ; drug therapy ; Myoglobin ; blood ; Rats ; Troponin T ; blood

Sepsis is a common disease in critical patients, which may lead to myocardial damage, thereby aggravating the severity of the patients' condition, and causing adverse prognosis. How to detect sepsis with myocardial injury as early as possible, and use corresponding treatment measures on time are essential. Cardiac troponin I (cTnI), brain natriuretic peptide (BNP), myoglobin (Mb), MB isoenzyme of creatine kinase (CK-MB) and other traditional cardiac markers are easily affected by the complications of other critical diseases, thus the diagnostic value of those markers for myocardial injury of sepsis is reduced. In recent years, there have been some studies on heart-type fatty acid binding protein (H-FABP), microRNA (miRNA), soluble triggering receptor expressed on myeloid cell-1 (sTREM-1), high mobility group protein B1 (HMGB1), neutrophil gelatinase-associated lipocalin (NGAL), histone and other new biomarkers of myocardial injury in septic patients. This article reviewed the value of these unconventional cardiac markers in the diagnosis of sepsis-induced myocardial injury, with the hope to provide some help for clinic.
Biomarkers ; Creatine Kinase, MB Form ; Humans ; Myocardial Infarction ; Myoglobin ; Natriuretic Peptide, Brain ; Sepsis ; Troponin I