OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective:To investigate the short-term pulmonary function outcomes in children with congenital diaphragmatic hernia (CDH) following surgery and analyze the influencing factors of poor outcomes.Methods:This study retrospectively enrolled 81 children who had undergone surgery for CDH and were discharged after recovery at the Department of Neonatal Surgery, Children's Hospital of Capital Institute of Pediatrics from January 2020 to June 2023. All children had pulmonary function tests before discharge, 6 months to 2 year after discharge. Changes in the pulmonary function parameters at different time points were compared. Based on the results of the final pulmonary function test after discharge, these patients were categorized into a favorable outcome group (32 cases) with normal pulmonary function and an unfavorable outcome group (49 cases) with pulmonary dysfunction. Clinical data of the two groups were compared using two independent samples t-test, rank-sum test, Chi-square test, or Fisher's exact test. Logistic regression analysis was used to explore the factors influencing pulmonary function outcomes. Results:A total of 81 cured and discharged CDH children were included in this study, comprising 34 males (42.0%) and 47 females (58.0%). The first two pulmonary function tests were performed at a mean postnatal age of (30.1±14.1) d (14-75 d) and (8.3±1.3) months (4 months and 14 d to 12 months), respectively. Pre-discharge pulmonary function tests revealed that 13 cases (16.0%) had nearly normal pulmonary function, while 68 cases (84.0%) showed pulmonary function abnormalities with seven cases of restrictive ventilatory dysfunction, 56 cases of obstructive ventilatory dysfunction, and five cases of mixed ventilatory dysfunction. In the children with abnormal pulmonary function before discharge, their second pulmonary function tests showed that some parameters including tidal volume [(7.49±1.35) ml/kg vs. (8.02±2.21) ml/kg], the ratio of time to peak tidal expiratory flow and expiratory time [(23.21±4.95)% vs. (26.50±5.48)%], the ratio of volume to peak expiratory flow and expiratory volume [(26.41±5.79)% vs. (27.55±5.20)%], respiratory system compliance per kg body weight during single occlusion [(0.93±0.22) ml/(cmH 2O·kg) vs. (0.96±0.25) ml/(cmH 2O·kg), 1 cmH 2O=0.098 kPa], functional residual capacity [(52.18±17.83) ml vs. (126.39±26.73) ml], and respiratory system resistance in single occlusion condition [(0.06±0.02) cmH 2O/(ml·s) vs. (0.05±0.01) cmH 2O/(ml·s)] improved after discharge ( t values were－2.41,－6.14,－7.68,－2.26,－18.94, and 4.87, all P<0.05). Eight children with obstructive ventilatory dysfunction were followed up for two years after surgery, of which three had normal lung function and five still showed mild to moderate obstructive ventilatory dysfunction. Logistic regression analysis indicated that liver herniation, severe pulmonary hypertension (PH), low observed-to-expected lung-to-head ratio (o/e LHR), grade C/D diaphragmatic defect, and prolonged invasive ventilation were risk factors for poor pulmonary outcomes [ OR(95% CI) were 5.655(1.410-22.676), 5.610 (1.589-19.804),4.183 (1.234-14.180) and 1.195(1.074- 1.329), all P<0.05]. Conclusions:Although lung function parameters of CDH patients show certain improvement after surgery, many children still have mild to moderate obstructive ventilatory dysfunction, requiring long-term follow-up. Prenatal and postnatal indicators such as liver herniation, severe PH, and low o/e LHR can predict the pulmonary outcomes of children with CDH.

OBJECTIVE To investigate the effectiveness of resident clinical pharmacist-led medication therapy management （MTM） model in geriatric cardiology departments， and provide reference for optimizing resident pharmaceutical services. METHODS A retrospective cohort study was conducted， incorporating data from inpatients admitted to the Department of Cardiovascular Medicine in the Geriatric Medical Center of our hospital during March to August 2023 （conventional group， n＝ 903） and the same period in 2024 （MTM group， n＝963）. The conventional group received only standard pharmaceutical services （including prospective prescription review and retrospective order evaluation）， while the MTM group received additional resident clinical pharmacist-led interventions-such as medication reconciliation， personalized therapeutic drug monitoring （TDM）， standardized intravenous infusion management， and a four-stage closed-loop monitoring process-based on conventional care. The effectiveness of the MTM model was evaluated by comparing the primary outcome measures （e.g.， intravenous infusion rate， TDM target attainment rate） and secondary outcome measures [e.g.， incidence of drug-drug interactions （DDIs）， incidence of grade 3 or higher acute kidney injury， average length of hospital stay， cholesterol， and medication cost per capita] between the two groups. RESULTS Compared with the conventional group， in terms of primary outcome indexes： both the overall intravenous infusion rate and the use rate of acid-suppressive injection were significantly lowered in the MTM group （P＜0.05）； serum concentration target attainment rates for digoxin and vancomycin were increased significantly （P＜0.05）. For secondary outcome indexes， the MTM group exhibited significant decreases in the work incidence of grade 3 or higher acute kidney injury， the incidence of DDIs， the rate of patients leaving the hospital against medical advice， alanine amino-transferase， aspartate transferase and the per capita total medication cost （P＜0.05）. Additionally， there was a notable increase in the creatinine， estimated glomerular filtration rate and a significant shortening of the per capita length of hospital stay （P＜0.05）. CONCLUSIONS The resident clinical pharmacist-led MTM model can significantly optimize medication therapy processes， enhance medication safety and cost-effectiveness， thus playing a positive role in promoting rational drug use and improving patient outcomes.

Beta-amylases (BAMs), key enzymes in starch hydrolysis, play an important role in plant growth, development, and resistance to abiotic stress. To mine the saline-alkali tolerance-related BAM genes in alfalfa (Medicago sativa L.), we identified MsBAM genes in the whole genome. The physicochemical properties, phylogeny, gene structures, conserved motifs, secondary structures, promoter cis-acting elements, chromosome localization, and gene replication relationships of BAM gene family members were analyzed. RNA-seq and quantitative real-time PCR (qRT-PCR) were employed to analyze the expression patterns of BAM family members under saline-alkali stress. The results showed that 54 BAM genes were identified in the genome, which were classified into 8 subgroups according to the phylogenetic tree. The members of the same subgroup had similar gene structures except that those of subgroups 1 and 7 had large differences. Conserved motif analysis showed that all MsBAM proteins had a typical glycohydrolysis domain. The chromosome localization analysis showed that MsBAM gene family members were unevenly distributed on 27 chromosomes. The duplication of gene segments led to the increase in BAM gene number in alfalfa. The promoters of BAM genes contained a large number of elements in response to plant hormones and stress. Transcriptome data and qRT-PCR results showed that the expression levels of most MsBAM genes were up-regulated in response to saline-alkali stress. Under the saline-alkali stress, the expression levels of 28 genes, including MsBAM6, were up-regulated on days 1 and 7, and those of 5 genes, including MsBAM9, were up-regulated by over 2 folds. In addition, under salt-alkali stress, BAM activity and soluble sugar content were significantly increased. These results indicate that BAM genes play a key role in alfalfa in response to saline-alkali stress, laying a foundation for further research in this field.
Medicago sativa/physiology* ; beta-Amylase/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Stress, Physiological/genetics* ; Multigene Family ; Alkalies ; Plant Proteins/genetics*

Ischemic stroke(IS)is a disease caused by insufficient blood and oxygen supply to cerebral vessels,with the main clinical manifestations of hemiplegia,sensory disturbance,aphasia,and ataxia.Studies have shown that hypoxia-inducible factor 1α(HIF-1α),as the core regulatory element of oxygen homeostasis,can be rapidly activated under hypoxia/ischemia conditions,thereby playing an important role in the pathophysiology of IS.In recent years,more and more articles have shown that the active components of tradi-tional Chinese medicine,Chinese patent drugs,and compound traditional Chinese medicine prescriptions can effectively regulate the HIF-1α-related signaling pathway in the treatment of IS,but there is no systematic summary on regulation of the HIF-1α signaling pathway in the treatment of IS.Therefore,this article mainly summarizes the structure and physiological activity of HIF-1α and its mechanisms of action in IS and reviews related studies on Chinese medicine monomers and compound prescriptions in the treatment of IS in the past five years in China and globally.It is pointed out that the Chinese medicine monomers and compound prescriptions can repair brain tissue,alleviate brain tissue damage,and exert a therapeutic effect on IS by regulating the HIF-1α pathway to promote an-giogenesis,inhibit neuroinflammation and oxidative stress,promote energy metabolism,and repair blood-brain barrier damage.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective:To investigate the short-term pulmonary function outcomes in children with congenital diaphragmatic hernia (CDH) following surgery and analyze the influencing factors of poor outcomes.Methods:This study retrospectively enrolled 81 children who had undergone surgery for CDH and were discharged after recovery at the Department of Neonatal Surgery, Children's Hospital of Capital Institute of Pediatrics from January 2020 to June 2023. All children had pulmonary function tests before discharge, 6 months to 2 year after discharge. Changes in the pulmonary function parameters at different time points were compared. Based on the results of the final pulmonary function test after discharge, these patients were categorized into a favorable outcome group (32 cases) with normal pulmonary function and an unfavorable outcome group (49 cases) with pulmonary dysfunction. Clinical data of the two groups were compared using two independent samples t-test, rank-sum test, Chi-square test, or Fisher's exact test. Logistic regression analysis was used to explore the factors influencing pulmonary function outcomes. Results:A total of 81 cured and discharged CDH children were included in this study, comprising 34 males (42.0%) and 47 females (58.0%). The first two pulmonary function tests were performed at a mean postnatal age of (30.1±14.1) d (14-75 d) and (8.3±1.3) months (4 months and 14 d to 12 months), respectively. Pre-discharge pulmonary function tests revealed that 13 cases (16.0%) had nearly normal pulmonary function, while 68 cases (84.0%) showed pulmonary function abnormalities with seven cases of restrictive ventilatory dysfunction, 56 cases of obstructive ventilatory dysfunction, and five cases of mixed ventilatory dysfunction. In the children with abnormal pulmonary function before discharge, their second pulmonary function tests showed that some parameters including tidal volume [(7.49±1.35) ml/kg vs. (8.02±2.21) ml/kg], the ratio of time to peak tidal expiratory flow and expiratory time [(23.21±4.95)% vs. (26.50±5.48)%], the ratio of volume to peak expiratory flow and expiratory volume [(26.41±5.79)% vs. (27.55±5.20)%], respiratory system compliance per kg body weight during single occlusion [(0.93±0.22) ml/(cmH 2O·kg) vs. (0.96±0.25) ml/(cmH 2O·kg), 1 cmH 2O=0.098 kPa], functional residual capacity [(52.18±17.83) ml vs. (126.39±26.73) ml], and respiratory system resistance in single occlusion condition [(0.06±0.02) cmH 2O/(ml·s) vs. (0.05±0.01) cmH 2O/(ml·s)] improved after discharge ( t values were－2.41,－6.14,－7.68,－2.26,－18.94, and 4.87, all P<0.05). Eight children with obstructive ventilatory dysfunction were followed up for two years after surgery, of which three had normal lung function and five still showed mild to moderate obstructive ventilatory dysfunction. Logistic regression analysis indicated that liver herniation, severe pulmonary hypertension (PH), low observed-to-expected lung-to-head ratio (o/e LHR), grade C/D diaphragmatic defect, and prolonged invasive ventilation were risk factors for poor pulmonary outcomes [ OR(95% CI) were 5.655(1.410-22.676), 5.610 (1.589-19.804),4.183 (1.234-14.180) and 1.195(1.074- 1.329), all P<0.05]. Conclusions:Although lung function parameters of CDH patients show certain improvement after surgery, many children still have mild to moderate obstructive ventilatory dysfunction, requiring long-term follow-up. Prenatal and postnatal indicators such as liver herniation, severe PH, and low o/e LHR can predict the pulmonary outcomes of children with CDH.

Atherosclerosis is a chronic vascular inflammatory disease caused by abnormal lipid metabolism.The formation of lipid-rich foam cells acts as the initial trigger for development of atherosclerotic lesions.Recent studies have shown that lipophagy,a form of selective autophagy,can selectively degrade lipid droplets stored intracellularly and promote cholesterol efflux through the autophagic lysosomal pathway.As a result,intracellular lipid accumulation is re-duced and foaming is inhibited,making lipophagy a potential new target for current anti-atherosclerosis therapy.This arti-cle reviews the crucial role and molecular mechanism of lipophagy in the link between lipid metabolism and atherosclero-sis.Its objective is to outline the regulatory mechanism of lipophagy and present fresh insights for the treatment of athero-sclerotic diseases.

OBJECTIVE To establish an HPLC method for the separation of enantiomers of farrerol, and apply it to the determination of the content of enantiomers in Rhododendri Daurici Folium and Rhododendron Micranthum. METHODS HPLC was used to separate the farrerol enantiomers, and the chromatographic conditions of chiral column type, mobile phase ratio, flow rate, and column temperature were optimized. The thermodynamic separation of farrerol enantiomers was discussed. Thermodynamic parameters such as enthalpy change, entropy change, enthalpy change and entropy change were calculated. And the contents of two enantiomers in Rhododendri Daurici Folium and Rhododendron Micranthum were determined under the optimum resolution conditions. RESULTS The optimum separation conditions for two enantiomers of farrerol were determined as follows: Chiralcel OJ-RH(4.6 mm×150 mm, 5 μm), equilibrium elution of acetonitrile-water(40∶60), the flow rate of 0.5 mL·min–1, the column temperature of 25 ℃, and the detection wavelength of 295 nm. Under the optimum separation conditions, the resolution of farrerol enantiomers reached 1.5, indicating that the two enantiomers of the farrerol could be completely separated. When the column temperature was between 20 ℃ and 35 ℃, the separation factor decreased with the increase of temperature. The lnα of the two enantiomers of farrerol showed a good linear relationship with 1/T, and the chiral reselution process was controlled by enthalpy. The enantiomer separation method of farrerol was applied to the determination of farrerol enantiomer in Chinese medicinal materials of Rhododendri Daurici Folium and Rhododendron Micranthum. The linear relationship between the two enantiomers of farrerol were good in the range of 0.718–57.44 μg·mL–1 and 1.28–102.24 μg·mL–1, respectively. And the contents of the two enantiomers of farrerol in Rhododendri Daurici Folium were 0.228 2 and 0.466 2 mg·g–1, respectively. And the contents of the two enantiomers of farrerol in Rhododendron Micranthum were 0.416 8 and 0.707 3 mg·g–1, respectively. CONCLUSION This method is simple, efficient and suitable for the determination of farrerol enantiomers in traditional Chinese medicine.