Objective To determine the material basis of the antioxidant activity of Mori Folium by examining the spec-trum-effect relationship.Methods High-performance liquid chromatography(HPLC)was utilized to establish the fingerprints of Mori Folium.The antioxidant activity of Mori Folium was assessed using the 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging assay and other related indicators.The spectrum-effect relationship of antioxidation was analyzed using gray relational analysis,bivariate correlation analysis,and partial least squares regression analysis.Molecular docking techniques were employed to predict potential interaction targets.Results HPLC fingerprints for 13 batches of Mori Folium were established,and thirteen common peaks were marked,with similarities ranging from 0.932 to 0.998.Nine common peaks were identified by comparing them to reference substances.Differences in antioxidant activity were observed among the different batches of Mori Folium.Based on the analysis of the spectrum-effect relationship,chemical components such as chlorogenic acid,cryptochlorogenic acid,rutin,and iso-chlorogenic acid B were found to contribute significantly to the antioxidant activity.These components may exert their effects by binding to several antioxidant protein targets,such as XOD,NO-1,and PPAR-α.This implies that Mori Folium might exert its an-tioxidant action via multiple components and targets.Conclusions By integrating the fingerprint and antioxidant activity of Mori Folium,the contributions of individual components to its antioxidant activity were determined.This study provides an experi-mental basis for elucidating the substances responsible for the antioxidant activity of Mori Folium and for establishing quality con-trol methods.

Objective To evaluate the correlation between the changes of vascular density in deep and shallow layers,retinal hyperreflexia and the therapeutic response of diabetic macular edema(DME).Methods Retrospectively selected DME patients(45 cases and 59 eyes)who visited the Department of Ophthalmology from April 2020 to November 2023 as the experimental group.Compare the change of deep and superficial blood vessel density and retinal hyperreflective points before and after treatment of the patients.The correlation between each index and poor response to anti-vascular endothelial growth factor(VEGF)treatment with DME was analyzed using the Pearson test.The value of baseline deep retinal capillary plexus(DCP),central macular retinal thickness(CMT),number of high-reflective foci(HRF)in the retina,and blood flow density(FD300-VD)in diagnosing poor response to anti-VEGF therapy in DME was analyzed using the subject operating characteristic curve(ROC).Results Compared with pre-treatment,patients'superficial retinal capillary plexus(SCP),DCP,FD300-VD,and deep-superficial flow ratio(DSFR)increased and CMT thickness significantly decreased after treatment(P<0.05).Pearson's correlation test showed that the outcome of patients with poor response to anti-VEGF therapy was negatively correlated with baseline SCP-VD,DCP-VD,DSFR,and FD300-VD(r=-0.458,-0.433,-0.604,and-0.452,P<0.05)and positively correlated with CMT(r=0.427,P<0.05).The results of multifactorial logistic regression analysis showed that a rise in SCP,DCP,FD300-VD,and DSFR,and a decrease in CMT were corre-lates affecting the response to anti-VEGF therapy in DME(OR=0.285,0.272,0.291,0.268,2.821,P<0.05).The results of ROC curve analysis showed that the AUCs of baseline DCP,CMT,HRF quantity,and FD300-VD were 0.918,0.934,0.947,and 0.927,respectively,which were of good value in diagnosing poor response to anti-VEGF therapy in DME.Conclusion Morphologic indicators such as changes in the density of deep and superfi-cial blood vessels and retinal hyperreflective spots have good application value in assessing the response to DME treatment and can assist in clinical treatment.

ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection， as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022， among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment （2022 edition） were enrolled， and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system， with stages 0 — 4 for inflammation grade （G） and stages 0 — 4 for fibrosis degree （S）， and the patients were divided into groups based on the presence of significant necroinflammation （≥G2） and significant liver fibrosis （≥S2）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors， and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled， among whom 61 （22.5%） had significant necroinflammation （≥G2） and 124 （45.8%） had significant liver fibrosis （≥S2）. The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L （for male patients） or ≥19 U/L （for female patients） （odds ratio ［OR］=2.69， 95% confidence interval ［CI］： 1.39 — 5.21， P=0.003）， HBV DNA ≥2 000 IU/mL （OR=2.75， 95%CI： 1.38 — 5.48， P=0.004）， and liver stiffness measurement （LSM） ≥6.0 kPa （OR=4.57， 95%CI： 2.17 — 9.62， P<0.001） were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL （OR=1.82， 95%CI： 1.01 — 3.32， P=0.049） and LSM ≥6.0 kPa （OR=2.06， 95%CI： 1.23 — 3.43， P=0.006） were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection， a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective:To investigate the relation between temporal expression changes of proline-rich transmembrane protein 2 ( PRRT2) gene and clinical progression of PRRT2-related paroxysmal disorders (PRPDs). Methods:A retrospective analysis was performed; 19 patients with PRPDs admitted to Department of Neurology, Second Affiliated Hospital of Guangzhou Medical University from July 2021 to July 2024 were enrolled; their clinical data, including onset age and disease progression, were collected. Using Bgee database, the PRRT2 gene expressions in different age groups were analyzed to explore their relations with clinical progression. Results:Among the 19 patients, 8 were diagnosed as having infantile convulsion with choreoathetosis (ICCA), 1 patient as having infantile convulsion, and 10 as having paroxysmal kinesigenic dyskinesia (PKD). Among patients with ICCA, the disease course was divided into two stages: in infantile period, it manifested as infantile convulsions at the onset, with an onset age of (5.75±1.03) months, ranged 4-7 months; in early childhood, no seizures were noted, enjoying a silent period and lasting for a period ranged 7-15 years; subsequently, the disease relapsed during adolescent, presenting as dyskinesia, with an onset age of (11.75±3.11) years, ranged 8-16 years. Among patients with PKD, onset age was (10.40±3.17) years, ranged 5-17 years. PRRT2 expression peaked before 1 year old, declined to the lowest level at 10 years old, and then gradually increased, reaching a second peak at 17 years old; PRRT2 expression demonstrated bimodal peaks during early childhood and adolescence. Conclusion:PRPDs progression shows a certain consistency with the temporal change of PRRT2 gene expression.

Objective To determine the material basis of the antioxidant activity of Mori Folium by examining the spec-trum-effect relationship.Methods High-performance liquid chromatography(HPLC)was utilized to establish the fingerprints of Mori Folium.The antioxidant activity of Mori Folium was assessed using the 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging assay and other related indicators.The spectrum-effect relationship of antioxidation was analyzed using gray relational analysis,bivariate correlation analysis,and partial least squares regression analysis.Molecular docking techniques were employed to predict potential interaction targets.Results HPLC fingerprints for 13 batches of Mori Folium were established,and thirteen common peaks were marked,with similarities ranging from 0.932 to 0.998.Nine common peaks were identified by comparing them to reference substances.Differences in antioxidant activity were observed among the different batches of Mori Folium.Based on the analysis of the spectrum-effect relationship,chemical components such as chlorogenic acid,cryptochlorogenic acid,rutin,and iso-chlorogenic acid B were found to contribute significantly to the antioxidant activity.These components may exert their effects by binding to several antioxidant protein targets,such as XOD,NO-1,and PPAR-α.This implies that Mori Folium might exert its an-tioxidant action via multiple components and targets.Conclusions By integrating the fingerprint and antioxidant activity of Mori Folium,the contributions of individual components to its antioxidant activity were determined.This study provides an experi-mental basis for elucidating the substances responsible for the antioxidant activity of Mori Folium and for establishing quality con-trol methods.

Objective To investigate the incidence and adverse prognosis of late onset sepsis(LOS)in neonates in neonatal intensive care unit(NICU).Methods A retrospective study was conducted to collect and analyze the peri-natal condition,underlying diseases,invasive procedures,and adverse prognosis of neonates in NICU of a regional maternal and child healthcare hospital from 2019 to 2023.According to whether LOS occurred during hospitaliza-tion,neonates were divided into LOS group and non-LOS group.The LOS group was divided into 5 subgroups based on whether invasive procedures were performed:LOS plus umbilical vein catheter(UVC)group,LOS plus peripherally inserted central catheter(PICC)group,LOS plus sequential catheter group,LOS plus tracheal intuba-tion group,and LOS plus lumbar puncture group,the relationship between LOS and adverse prognosis was ana-lyzed.Results Among 2 945 neonates in NICU,354(12.02％)developed LOS.Comparison between LOS groups and non-LOS group were as follows:in term of perinatal condition of neonates,there were statistically significant difference in weight,gestational age,and whether they were twins between the two groups(all P＜0.001);in term of underlying diseases,there were statistically significant differences in the number of cases of maternal gestational hypertension,neonatal asphyxia,neonatal congenital heart disease,neonatal ventricular dilation,neonatal pneumo-nia,neonatal hyperthyrotropinemia,and neonatal anemia,as well as five invasive procedures between the two groups(all P＜0.05).Compared with the non-LOS group,the incidences of retinopathy of prematurity(ROP),neonatal necrotizing enterocolitis(NNEC),bronchopulmonary dysplasia(BPD),and neonatal respiratory distress syndrome(NRDS)in LOS group were all higher(all P＜0.001).Regression analysis showed that compared with the non-LOS groups,the risk of ROP increased in the LOS group and its subgroups,with the LOS plus sequential catheter group having a 2.27-fold higher risk of ROP than non-LOS group;the risk of NNEC increased in the LOS group and its subgroups,with the LOS plus UVC group having an 8.29-fold higher risk of NNEC than the non-LOS group.Except for the LOS plus UVC group,the risk of BPD increased in the LOS group and other subgroups,with the LOS plus PICC group and LOS plus sequential catheter group having 4.68-and 4.64-fold higher risk of BPD than the non-LOS group,respectively;the risk of NRDS in the LOS plus PICC group was 6.84-fold higher than the non-LOS group(all P＜0.05).The top three pathogens causing LOS were coagulase negative Staphylococcus,Klebsiella pneumoniae,and Escherichia coli.Conclusion LOS can significantly increase the risks of ROP,NNEC,BPD,and NRDS.LOS plus invasive procedures can further increase the risk of adverse prognosis.

BACKGROUND:The energy metabolism and polarization state of macrophages play a crucial role in the progression of atherosclerosis.Traditional Chinese Medicine(TCM)has shown significant therapeutic potential for prevention and treatment of atherosclerosis by regulating macrophage metabolic pathways.OBJECTIVE:To review the research progress in AMP-activated protein kinase regulation of macrophage energy metabolism and polarization and explore the mechanism of TCM in the prevention and treatment of atherosclerosis.METHODS:A computerized search was conducted on the databases including Web of Science,PubMed,and CNKI,covering relevant literature up to June 2024.The search terms were"AMPK,fatty acid oxidation,macrophage polarization,Traditional Chinese Medicine,atherosclerosis,coronary heart disease"in Chinese and English.A total of 62 articles were finally included for review.RESULTS AND CONCLUSION:The shiftin macrophage energy metabolism from oxidative phosphorylation to glycolysis plays a key role in the progression of atherosclerosis.The activation of AMP-activated protein kinase in macrophages promotes fatty acid oxidation and M2 polarization,exerting anti-inflammatory effects and stabilizing arterial plaques.TCM monomers(such as ginseng,astragalus,and polygonatum)and compounds(such as Huanglian Jiedu Decoction,Yangxin Shumai Granules,and Tiaogan Daozhuo Formula)influence macrophage metabolism and cellular function by regulating the AMP-activated protein kinase pathway and intervening in multiple signaling pathways,such as nuclear factor-κB,peroxisome proliferator-activated receptor γ,and mammalian target of rapamycin,thereby achieving therapeutic effects.Future research should focus on the interactions between AMP-activated protein kinase,metabolism,and polarization pathways,as well as how TCM exerts its therapeutic effects through these pathways,providing new strategies for the treatment of atherosclerosis.

Objective To investigate the incidence and adverse prognosis of late onset sepsis(LOS)in neonates in neonatal intensive care unit(NICU).Methods A retrospective study was conducted to collect and analyze the peri-natal condition,underlying diseases,invasive procedures,and adverse prognosis of neonates in NICU of a regional maternal and child healthcare hospital from 2019 to 2023.According to whether LOS occurred during hospitaliza-tion,neonates were divided into LOS group and non-LOS group.The LOS group was divided into 5 subgroups based on whether invasive procedures were performed:LOS plus umbilical vein catheter(UVC)group,LOS plus peripherally inserted central catheter(PICC)group,LOS plus sequential catheter group,LOS plus tracheal intuba-tion group,and LOS plus lumbar puncture group,the relationship between LOS and adverse prognosis was ana-lyzed.Results Among 2 945 neonates in NICU,354(12.02％)developed LOS.Comparison between LOS groups and non-LOS group were as follows:in term of perinatal condition of neonates,there were statistically significant difference in weight,gestational age,and whether they were twins between the two groups(all P＜0.001);in term of underlying diseases,there were statistically significant differences in the number of cases of maternal gestational hypertension,neonatal asphyxia,neonatal congenital heart disease,neonatal ventricular dilation,neonatal pneumo-nia,neonatal hyperthyrotropinemia,and neonatal anemia,as well as five invasive procedures between the two groups(all P＜0.05).Compared with the non-LOS group,the incidences of retinopathy of prematurity(ROP),neonatal necrotizing enterocolitis(NNEC),bronchopulmonary dysplasia(BPD),and neonatal respiratory distress syndrome(NRDS)in LOS group were all higher(all P＜0.001).Regression analysis showed that compared with the non-LOS groups,the risk of ROP increased in the LOS group and its subgroups,with the LOS plus sequential catheter group having a 2.27-fold higher risk of ROP than non-LOS group;the risk of NNEC increased in the LOS group and its subgroups,with the LOS plus UVC group having an 8.29-fold higher risk of NNEC than the non-LOS group.Except for the LOS plus UVC group,the risk of BPD increased in the LOS group and other subgroups,with the LOS plus PICC group and LOS plus sequential catheter group having 4.68-and 4.64-fold higher risk of BPD than the non-LOS group,respectively;the risk of NRDS in the LOS plus PICC group was 6.84-fold higher than the non-LOS group(all P＜0.05).The top three pathogens causing LOS were coagulase negative Staphylococcus,Klebsiella pneumoniae,and Escherichia coli.Conclusion LOS can significantly increase the risks of ROP,NNEC,BPD,and NRDS.LOS plus invasive procedures can further increase the risk of adverse prognosis.

BACKGROUND:The energy metabolism and polarization state of macrophages play a crucial role in the progression of atherosclerosis.Traditional Chinese Medicine(TCM)has shown significant therapeutic potential for prevention and treatment of atherosclerosis by regulating macrophage metabolic pathways.OBJECTIVE:To review the research progress in AMP-activated protein kinase regulation of macrophage energy metabolism and polarization and explore the mechanism of TCM in the prevention and treatment of atherosclerosis.METHODS:A computerized search was conducted on the databases including Web of Science,PubMed,and CNKI,covering relevant literature up to June 2024.The search terms were"AMPK,fatty acid oxidation,macrophage polarization,Traditional Chinese Medicine,atherosclerosis,coronary heart disease"in Chinese and English.A total of 62 articles were finally included for review.RESULTS AND CONCLUSION:The shiftin macrophage energy metabolism from oxidative phosphorylation to glycolysis plays a key role in the progression of atherosclerosis.The activation of AMP-activated protein kinase in macrophages promotes fatty acid oxidation and M2 polarization,exerting anti-inflammatory effects and stabilizing arterial plaques.TCM monomers(such as ginseng,astragalus,and polygonatum)and compounds(such as Huanglian Jiedu Decoction,Yangxin Shumai Granules,and Tiaogan Daozhuo Formula)influence macrophage metabolism and cellular function by regulating the AMP-activated protein kinase pathway and intervening in multiple signaling pathways,such as nuclear factor-κB,peroxisome proliferator-activated receptor γ,and mammalian target of rapamycin,thereby achieving therapeutic effects.Future research should focus on the interactions between AMP-activated protein kinase,metabolism,and polarization pathways,as well as how TCM exerts its therapeutic effects through these pathways,providing new strategies for the treatment of atherosclerosis.