Herba Epimedii (named Yinyanghuo in Chinese) of the family Berberidaceae is one of the most famous traditional Chinese medicines (TCMs) recorded in the pharmacopoeia of the People's Republic of China.Total flavonoids of Epimedium (TFE) are considered to be its active components.TFE content was measured by ultraviolet method and its representative constituents,icariin and epimedin C,were determined by high performance liquid chromatography.The test results from 36 samples of 4 species showed that the contents differed significantly in different species.The average data of the summation (icariin and epimedin C) content were 20.83,7.61,14.43,23.29 mg/g in Epimedium pubescens Maxim.,E.koreanum Nakai.,E.brevicornum Maxim.,E.sagittatum (Sieb.Et Zucc.) Maxim.,respectively.Both E.sagittatum and E.pubescens performed better than the other two batches.E.sagittatum hardly has any circulation in Chinese herbal medicine market.The results showed that E.pubescens,which had much more amounts of icariin,epimedin C and TFE than those of other species,has a better quality and may be considered as potential anti-osteoporosis drug.

OBJECTIVETo investigate the TNF-alpha induced apoptosis of U937 cells, the expression, degradation and subcellular localization of IkappaB-alpha, and its degradation mechanism.

METHODChanges and subcellular loca-lization of IkappaB-alpha were observed by fluorescence microscopy, expression and degradation of IkappaB-alpha protein with N-tosyl-L-phenylalanylchloromethyl ketone (TPCK protease inhibitor) blocking test and apoptosis of U937 cell by flow cytometry.

RESULTS(1) immunolfluorescence assay showed that IkappaB-alpha localized in cytoplasm only. (2) The level of IkappaB-alpha protein was downregulated after TNF-alpha stimulation, flow cytometry also confirmed the downregulation. (3) The downregulation of IkappaB-alpha protein levels in TNF-alpha induced apoptosis was partially inhibited by TPCK. (4) The apoptosis rate of U937 cells induced by TNF-alpha was (60.73 +/- 1.61)%.

CONCLUSION(1) Degradation of IkappaB-alpha protein during TNF-alpha induced apoptosis of U937 cells suggested the activation of NF-kappaB. (2) TPCK sensitive protease plays an important role in the degradation of IkappaB-alpha protein. (3) TPCK sensitive protease also involved in the apoptosis of U937 cells induced by TNF-alpha.

Animals ; Embryonic Stem Cells ; virology ; Gene Expression Regulation, Enzymologic ; Histone Deacetylase 6 ; Histone Deacetylases ; biosynthesis ; genetics ; Infection ; genetics ; pathology ; virology ; Mice ; Mice, Knockout

Objective:To explore the diagnostic accuracy and application value of 3.0 T non-contrast coronary magnetic resonance angiography (CMRA) in evaluating coronary artery in children with Kawasaki disease (KD).Methods:From May 2019 to January 2022, 75 children diagnosed with KD in our hospital were enrolled. All the patients underwent CMRA and transthoracic echocardiography (TTE) in one week, twenty-six of whom underwent coronary CT angiography (CCTA) or invasive coronary angiography (ICA) within two weeks. The diagnostic performance of CMRA and TTE was evaluated with CCTA/ICA as reference standard by per-patient basis, per-vessel basis, per-segment basis. Sensitivity and specificity of CMRA and TTE was compared by paired chi square test.The distribution of coronary artery aneurysm (CAA), thrombosis and other pathological changes of coronary artery were recorded and compared between two methods. The patients′ height and weight were collected to calculate the Z value. Z value>2.5 was defined as CAA.Results:All patients successfully completed CMRA examinations. Among the 26 patients, the sensitivity of CMRA was significantly higher than that of TTE by per coronary artery[97.7%(43/44)vs.84.1%(37/44), χ2=4.17, P<0.05]. CMRA showed a higher sensitivity than that of TTE both by proximal segments and middle/distal segments [97.7%(43/44)vs. 84.1%(37/44), 100%(21/21) vs. 52.4%(11/21), χ2=10.08, 7.11, both P<0.05). A total of 115 CAAs was found by CMRA, while only 87 (75.7%) CAAs were observed by TTE. Of the 28 (24.3%) CAAs missed by TTE, 16 (57.1%) were located in right coronary artery (RCA), 2(7.1%) in left main coronary artery, 7(25.0%) in left anterior ascending coronary artery (LAD) and 3(10.7%) in left circumflex coronary artery (LCX). Eleven (39.3%) missed CAAs by TTE were located in the proximal segment of RCA, LMCA, LAD and LCX, and 17 (60.7%) missed CAAs were located in the middle and distal segments. TTE missed coronary thrombosis in 5 patients compared with CMRA. Conclusions:3.0 T non-contrast CMRA is non-invasive and non-radiation, and the image quality can meet the needs of diagnosis, especially for detection of CAAs in RCA or in middle and distal segments of coronary artery in KD patients.

Objective: To evaluate the safety and efficacy of preoperative autologous blood donation (PABD) under anesthesia monitoring in elective surgical procedures, and to provide scientific data for promoting its clinical application. Methods: 1) A total of 1 164 patients scheduled for elective surgery and met the criteria for stored autologous blood transfusion in our hospital from March 2022 to September 2023 were enrolled. Prior to surgery, stored autotransfusion was performed under anesthesia monitoring. During the operation, blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO ) and other basic life indicators before and after blood collection were recorded and analyzed. Adverse reactions during blood collection were documented, and potential influencing factors were analyzed. 2) The autologous transfusion group (experimental group, patients receiving intraoperative autologous blood reinfusion) was compared with the allogeneic transfusion group (control group, patients without PABD during the same period) using propensity score matching. The length of hospital stay, transfusion-related costs, perioperative hemoglobin (Hb), hematocrit (Hct), platelet count (Plt) and coagulation function were compared between the two groups after matching. Results: 1) Three patients (0.26%) had adverse reactions during blood collection. Autologous blood transfusion was performed in 443 patients (38.1%) during or after operation, with no adverse reaction during blood transfusion. 2) The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of patients after blood collection were lower than before blood collection, and the SpO was higher than before blood collection, with statistically significant differences (P<0.05); There was no significant difference in heart rate before and after blood collection (P>0.05); Our analysis found that age, gender, blood collection volume, department, or mild-to-moderate circulatory system complications didn’t significantly affect BP, HR and SpO fluctuations (P>0.05). 3) The experimental group had shorter hospital stays and lower transfusion costs than the control group (P<0.05). 4) No significant differences were observed in Hb, Hct, Plt levels or coagulation function (PT, APTT) between the two groups after operation (P>0.05). The hospitalization duration and transfusion related expenses in the experimental group were lower than those in the control group (P<0.05). Conclusion: PABD under anesthesia monitoring is safe and feasible in elective surgeries across diverse patient groups and surgical fields. It reduces the costs and conserves blood resources, which is worthy of further promotion.

Objective To prepare and optimize the formulation of Albumin nanoparticles loading PROTAC molecule and observe the inhibition effect of nanoparticles on the proliferation and NAD⁺ metabolism of glioma cells. Methods Albumin nanoparticles loading NPT-B2 were prepared and characterized with a thermal driving method, and the prescription was optimized. An HPLC method was established to determine the content of NPT-B2. The proliferation inhibition of NPT-B2 and B2-BSA-NPs on U251 cells were investigated by the CCK8 method, and the degradation effects of NPT-B2 and B2-BSA-NPs on NAMPT in glioma cells were investigated by western blotting. Results The HPLC method was stable, with good linearity, precision, and recovery rate. The nanoparticles had a particle size of about 55.48 nm, a potential of about −12.9 mV, an encapsulation rate of about 94.74%, and a drug loading amount of about 8.61%. The IC₅₀ of NPT-B2 on glioma cells was 61.16 nmol/L, which had a degradation effect on NAMPT. The IC₅₀ of B2-BSA-NPs on glioma was 41.21 nmol/L, which had a very significant degradation effect on NAMPT. Conclusion Albumin nanoparticles loading PROTAC molecules were constructed. The prescription was optimized to improve the drug encapsulation rate, and the low water solubility of PROTAC molecule was improved, which had a significant inhibitory effect on the proliferation and NAD⁺ energy metabolism of glioma cells.

Humans ; Child ; Risk Factors ; Adipose Tissue

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.

ObjectiveTo assess the level of internal exposure to PCP in a community population in Shanghai， to investigate the factors affecting the level of PCP， and to analyze the correlation between the exposure and thyroid hormone levels. MethodsA total of 464 residents of a community in Shanghai were selected as the study subjects. A questionnaire survey was conducted to obtain the demographic information， dietary situation， lifestyle and behavioral habits， and disease history of the individuals， and blood samples were collected. Gas chromatography-electron trap was applied to determine the PCP levels in serum. Multicategorical logistic regression analysis was used to analyze the possible influencing factors of PCP exposure in humans. Thyroid hormone levels were used as the dependent variable and serum PCP as the independent variable. Multiple linear regression analysis was used to assess the association between PCP and thyroid hormones in the community population after controlling the confounding factors such as age， gender， literacy， annual personal income， and chronic diseases. ResultsThe detection rate of serum PCP in 464 subjects was 90.3%， and the median serum PCP level was 0.43 μg·L^-1. The differences in PCP levels among different age groups were statistically significant. There were no significant differences in PCP levels among different gender and BMI groups. The study of PCP exposure factors showed that age， frequency of using plastic products， consumption of freshwater fish， type of occupation， annual income， and consumption of tea or coffee were the potential influencing factors for PCP exposure. Among them， age， frequency of using plastic products， consumption of tea or coffee， and consumption of freshwater fish were positively associated with PCP levels， and annual personal income was negatively associated with it. The results of multiple linear regression analysis showed that among men， PCP levels were positively correlated with TSH （b=0.105， 95%CI：0.017‒0.313） and negatively correlated with FT4 （b=-0.026， 95%CI：-0.057‒0.004）， and among women， PCP levels were positively correlated with TSH （b=0.092， 95%CI：-0.211‒0.904） and FT3 （b=0.017， 95%CI：-0.058‒0.230） and negatively correlated with FT4 （b=-0.013， 95%CI：-0.011‒0.037）. ConclusionSerum PCP detection is common among community residents in Shanghai. Different demographic characteristics or behavioral habits may increase or decrease PCP exposure. PCP exposure then affects human thyroid hormone levels.