[Objective] To retrospectively analyse the serological characteristics of hemolytic transfusion reactions caused by Rh and Kidd antibodies, and to provide reference for safe, timely, and effective blood transfusion. [Methods] Two cases of patients with RhCcEe and Kidd blood type who experienced allogeneic transfusion at Dazhou Central Hospital were selected. A series of immunohematological tests were performed, including ABO, RhDCcEe and Kidd blood typing, unexpected antibody screening and identification, crossmatching, direct antiglobulin test, acid elution test, and capillary centrifugation to separate the patient's own red blood cells from donated red blood cells. [Results] Unexpected antibody screening, antibody identification, and direct antiglobulin test were positive in both patients. Case 1 had anti-Jk in the plasma, but no specific antibodies were found in the eluate. Case 2 had anti-c and E in the plasma, and anti-E was detected in the eluate. High-speed capillary centrifugation revealed corresponding antigen-positive erythrocytes at the distal end of the blood samples of both patients. [Conclusion] Case 1 received Kidd allogeneic red blood cells, and case 2 received RhCcEe allogeneic red blood cells, and both patients developed the corresponding unexpected antibodies, which led to the occurrence of immune haemolytic blood transfusion reaction.

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

BackgroundInsomnia， a common sleep disorder， is robustly associated with cardiovascular diseases， diabetes， and psychiatric disorders， substantially impairing quality of life. Although clinically commonly used medications are effective， long-term use may lead to drug resistance and dependence. While the efficacy of Ganmai Dazao Decoction in improving insomnia is definite， its underlying molecular mechanisms remain unclear. ObjectiveTo explore the active ingredients and core targets of Ganmai Dazao Decoction in the treatment of insomnia， systematically reveal its potential molecular pharmacological mechanism， and to provide references for clinical application. MethodsIn November 2024， the active ingredients and related targets of Ganmai Dazao Decoction were screened from the INPUT database. Insomnia-related datasets were acquired from the Gene Expression Omnibus （GEO） database， followed by differential expression analysis using GEO2R to identify differentially expressed genes （DEGs） associated with insomnia. The shared targets were obtained through Venn diagrams， and the protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape 3.9.1. Enrichment analyses were conducted on the shared targets using Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG）. The top 3 key active ingredients and the top 10 core targets in terms of node degree values were selected. Molecular docking and molecular dynamics simulation of receptors and ligands were performed using AutoDock 4.4.6， and the results were visualized using Pymol 3.0.3 to further verify the stability of the receptor-ligand complex system. ResultsA total of 337 active ingredients and 5 265 drug-related targets in Ganmai Dazao Decoction were retrieved， along with 1 061 insomnia-related DEGs. 287 shared targets were identified between Ganmai Dazao Decoction and insomnia. The traditional Chinese medicine-active ingredients-shared targets-disease network showed that quercetin， catechins and kaempferol were the key components of Ganmai Dazao Decoction in treating insomnia. These three components alleviate insomnia by acting on ten core targets， including nuclear factor kappa B inhibitor alpha （NFKBIA）， fibronectin 1 （FN1）， interleukin-6 （IL6）， protein c-Fos （FOS）， histone acetyltransferase p300 （EP300）， histone deacetylase 1 （HDAC1）， transcription factor Jun （JUN）， heat shock protein HSP 90-alpha 1 （HSP90AA1）， glyceraldehyde 3-phosphate dehydrogenase （GAPDH）， and interleukin-1 beta （IL1β）. GO and KEGG enrichment analyses indicated that Ganmai Dazao Decoction may alleviate insomnia through the IL17 signaling pathways， lipid and atherosclerosis signaling pathways， and other mechanisms. The results of molecular docking demonstrated strong binding affinity between the 3 key components and the 10 core targets of Ganmai Dazao Decoction. Molecular dynamics simulations further confirmed the stability of the quercetin-GAPDH， catechin-HDAC1 and kaempferol-EP300 complexes. ConclusionThe key components of Ganmai Dazao Decoction， namely quercetin， catechin， and kaempferol， exert therapeutic effects on insomnia by targeting 10 core proteins and modulating multiple pathways， including the IL17 signaling pathway， lipids and atherosclerotic-related pathways. ［Funded by Chengdu Medical College Level Scientific Research Project （number， CYZYB23-01）］

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.

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.