Fourteen flavonoids were isolated and purified from Epimedium sagittatum by various chromatography techniques such as macroporous adsorbent resin, silica gel, ODS, Sephadex LH-20, HW-40C and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 3′-hydroxy-baohuoside-Ⅱ (1), huazhongilexone-7-O-β-D-glucopyranoside (2), kaempferol-3-O-α-L-rhamnoside (3), baohuoside-Ⅱ (4), icariside-Ⅱ (5), kaempferol 3,7-di-O-α-L-rhamnopyranoside (6), (+)-aromadendrin (7), kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L-rhamnopyranoside (8), sagittatoside A (9), 2″-O-rhamnosyl icariside-II (10), apigenin-7-O-β-D-glucoside (11), quercetin 3-O-β-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (12), kaempferol (13), icariin (14). Among them, compound 1 is a new compound, while compounds 2, 6-8, 11, and 12 were isolated from E.sagittatum for the first time.

Humans ; Gemcitabine ; Neoplasms

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

OBJECTIVES: To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism. METHODS: A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats. RESULTS: Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05). CONCLUSIONS Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.
Animals ; Female ; Pregnancy ; Rats ; Body Weight ; Brain Injuries/prevention & control* ; Caspase 1 ; Inflammation/drug therapy* ; Interleukin-6 ; Interleukin-8 ; NF-E2-Related Factor 2 ; NLR Family, Pyrin Domain-Containing 3 Protein ; Flavonoids/therapeutic use*

Objective:To analyze the clinical characteristics of elderly acute pulmonary thromboembolism(APE)patients complicated with preexisting atrial fibrillation(AF)and the impact of preexisting AF on in-hospital adverse outcomes in elderly patients with APE.Methods:A retrospective analysis was performed on elderly APE patients with preexisting AF hospitalized in Beijing Anzhen Hospital, Capital Medical University between January 1, 2008 and December 31, 2021.We compared the comorbidities, symptoms, signs, laboratory test results and echocardiographic features, simplified pulmonary embolism severity index(sPESI)scores and adverse in-hospital outcomes between the preexisting AF group and the non-AF group.Logistic regression was used to analyze the risk factors of in-hospital adverse outcomes in elderly patients with APE.Results:A total of 240 patients diagnosed with APE were enrolled.There were 120 patients in the AF group and 120 patients in the non-AF group.For patients in the AF group and the non-AF group, the proportions with chronic heart failure were 38.3%(46/120)and 15.8%(19/120), the proportions with lower extremity deep vein thrombosis(DVT)were 36.7%(44/120)and 65.8%(79/120), the left ventricular ejection fractions(LVEF)were(59±10)% and(62±7)%, and hospital stays were(15±7)and(11±4)days, respectively, and the differences were statistically significant( χ2=15.381, 20.429, t=2.527, -4.710, all P<0.05). The incidences of in-hospital adverse outcomes in the AF group and the non-AF group were 4.2%(5/120)and 3.3%(4/120), respectively, with no significant difference( χ2=0.000, P=1.000). The overall incidence of in-hospital adverse outcomes was 3.8%(9/240). Multivariate Logistic regression analysis showed that elevated lactic acid was an independent risk factor for in-hospital adverse outcomes( OR=2.753, 95% CI: 1.367-5.542, P=0.005). However, AF( OR=2.880, 95% CI: 0.587-14.141, P=0.192)and sPESI score( OR=2.056, 95% CI: 0.904-4.673, P=0.086)were not associated with in-hospital adverse outcomes. Conclusions:Elderly APE patients with preexisting AF have a relatively low incidence of DVT, but a higher proportion have concurrent chronic heart failure and need a longer hospital stay.Elevated lactic acid is an independent risk factor for in-hospital adverse outcomes of elderly APE patients with preexisting AF.However, preexisting AF has no predictive value for in-hospital adverse outcomes in elderly patients with APE.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective:To establish the normal reference value of left ventricular function parameters by cadmium-zinc-tellurium (CZT) SPECT stress gated myocardial perfusion imaging (G-MPI) in low-likelihood of stable coronary artery disease (SCAD).Methods:From March 2022 to August 2022, 348 consecutive SCAD patients (146 males, 202 females, age (58±10) years) who underwent exercise or pharmacological stress G-MPI (CZT SPECT) in Beijing Anzhen Hospital, Capital Medical University were retrospectively recruited. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were acquired using quantitative gated SPECT (QGS) analysis. EDV and ESV were corrected by body surface area (BSA) to obtain EDV index (EDVI) and ESV index (ESVI), respectively. Independent-sample t test, one-way analysis of variance and Mann-Whitney U test were used for data analysis. The influences of EDV, ESV, EDVI, ESVI and LVEF were analyzed by multiple regressions for linear models. Results:There were 314 patients with low-likelihood of SCAD (128 males, 186 females, age (58±10) years) and 34 normal controls (18 males, 16 females, age (55±10) years). There were no significant differences of basic clinical characteristics and left ventricular function parameters in different genders between 2 groups ( z values: from -1.74 to -0.02, t values: from -1.16 to 1.17, all P>0.05). Using the 95% CI as the cut-off value for left ventricular function parameters in patients with a low-likelihood of SCAD, the upper limits of EDV, ESV, EDVI and ESVI in females and males were 84 and 111 ml, 30 and 44 ml, 47 and 54 ml/m 2, 17 and 21 ml/m 2, respectively, and the lower limit of LVEF in females and males were 58% and 55%, respectively. In the low-likelihood of SCAD group, the EDV ((58±13) vs (77±17) ml) and ESV ((16±7) vs (26±9) ml) of females were smaller than those of males ( t values: 10.65, 10.35, both P<0.001), while LVEF of females was higher than that of males ((72±7)% vs (67±6)%; t=-6.23, P<0.001). However, there were no significant differences in left ventricular function parameters among different age groups with the same gender ( F values: 0.12-2.19, all P>0.05). Based on multiple regression for linear models, the primary predictors of EDV, ESV and LVEF were gender and weight ( β values: from -0.380 to 0.358, all P<0.05). Conclusions:Normal reference values of left ventricular function parameters are established by CZT SPECT stress G-MPI in low-likelihood of SCAD patients. Left ventricular EDV and ESV of females are smaller than those of males, while LVEF of females is higher than that of males. The influence of gender on left ventricular function parameters should be considered in clinical practice.

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-β1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-β1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-β1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.
Mice ; Male ; Animals ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Epimedium/metabolism* ; Fibronectins/metabolism* ; Matrix Metalloproteinase 7/therapeutic use* ; Matrix Metalloproteinase 8/therapeutic use* ; Vimentin/metabolism* ; Interleukin-6/metabolism* ; Mice, Inbred C57BL ; Lung ; Collagen/metabolism* ; Bleomycin/toxicity* ; RNA, Messenger/metabolism* ; Cadherins/metabolism*

OBJECTIVE: Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. METHODS: Aeromonas isolates ( n = 79) collected from food samples were analyzed using concatenated gyrB- cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. RESULTS: Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [ tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr -1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. CONCLUSION The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.
Aeromonas/genetics* ; Animals ; Anti-Bacterial Agents/pharmacology* ; Caenorhabditis elegans ; Cefazolin ; China/epidemiology* ; Diarrhea ; Drug Resistance, Multiple, Bacterial/genetics* ; Genetic Variation ; Humans ; Peptide Hydrolases/genetics* ; Virulence/genetics*

Objective: This study was performed to compare the genetic diversity, virulence, and antimicrobial resistance of Methods: A total of 38 clinical strains and 19 strains from healthy individuals were isolated from the samples collected in Ma'anshan City, Anhui Province. Their taxonomy was investigated using concatenated Results: The 57 Conclusions The taxonomy, virulence properties, and antibiotic resistance of
Aeromonas/pathogenicity* ; Case-Control Studies ; Drug Resistance, Bacterial/genetics* ; Genetic Variation ; Humans ; Virulence Factors/genetics*