Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

A new iridoid was isolated from the Tabebuia avellanedae, its anti-myocardial injury activity was determined, and its mechanisms underlying inhibition of inflammation, regulation of oxidative stress and inhibition of apoptosis were explored. The dried inner bark of the Tabebuia avellanedae was extracted with boiling water, separated by liquid-liquid extraction, and purified by silica gel/ODS/Sephadex LH-20 column chromatography coupled with high-performance liquid chromatography (HPLC) to obtain avelladoid I (Avd I). The structure of Avd I was identified by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Cardiomyocyte injury model was established by 1 μg·mL^-1 doxorubicin. After treatment with 1-40 μmol·L^-1 of Avd I, the cell viability was evaluated by methyl thiazole tetrazolium (MTT) assay, and the lactate dehydrogenase (LDH) was measured. The inflammatory factor levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as well as the oxidative stress levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were detected. DCFH-DA staining was employed to observe the level of reactive oxygen species (ROS), AnnexinV-FITC/PI double stainings were performed to detect the apoptosis level, JC-1 single staining was used to measure the mitochondrial membrane potential level, and the Incell-Western assay was conducted to determine the apoptosis-related protein expression levels. The results showed that the cardiomyocyte injury was improved by 1-20 μmol·L^-1 of Avd I, and the IL-6 and IL-1β levels were decreased to near normal cell levels by 1 μmol·L^-1 Avd I. The ROS level was strongly reduced and the SOD level was highly increased by 1 μmol·L^-1 Avd I. In addition, 1 μmol·L^-1 Avd I significantly decreased the apoptosis level, the B-cell lymphoma-2 associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio and the cleaved cysteinyl aspartate specific proteinase 3 (cleaved caspase 3)/cysteinyl aspartate specific proteinase 3 (caspase 3) ratio. Therefore, Avd I could stimulate the cardiomyocyte proliferation, reduce the LDH level and inhibit inflammation levels through regulating the mitochondrial apoptotic pathway.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium(GIK)therapy on clinical outcomes in acute coronary syndrome(ACS)patients receiving reperfusion therapy. METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs)that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs). RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio[RR]0.57,95％confidence interval[95％CI]:0.35 to 0.94,P=0.03)and the risk of heart failure(RR 0.48,95％CI:0.25 to 0.95,P=0.04)and improved the left ventricular ejection fraction(LVEF)(mean difference[MD]2.12,95％CI:0.40 to 3.92,P=0.02)at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95％CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95％CI:1.74 to 47.29,P=0.009)and hypoglycemia(RR 6.50,95％CI:1.28 to 33.01,P=0.02)but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD)activity but not glutathione peroxidase(GSH-Px)or catalase(CAT)activity. CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.