OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Objective Magnetic resonance simulator(MR Sim)is a novel type of simulation equipment utilized in radiotherapy.Acceptance testing is an essential quality assurance procedure prior to the clinical use of the MR Sim.The report provides the detailed procedures and result analysis of acceptance testing for an MR Sim.Methods The acceptance testing scheme was developed following the recently published AAPM TG284 report and the NCC/T-RT 002-2023 guidelines.Quality control equipments such as ACR(American College of Radiology)large phantom and geometric distortion measurement phantom were used for evaluating various aspects of the MR Sim,including the effectiveness of shielding,the functionality of imaging system,the image quality,the performance of radio frequency coils,the geometric accuracy of large field imaging,the precision of external laser markings,the couch movement accuracy,and the image transmission accuracy.Results The shielding effectiveness at a frequency of 150 MHz exhibited an average value of 105 dB.All of 8 image quality indices,namely geometric accuracy,slice position accuracy,slice thickness accuracy,image uniformity,artifact ratio,signal-to-noise ratio,high-contrast spatial resolution,and low-contrast resolution,fell within recommended tolerances.The maximum geometric distortion observed across a 25 cm field of view was less than 2 mm.The errors in external laser markings and couch movement accuracy were both less than 1 mm.The couch levelness was less than 1°.Both radio frequency coils and image transmission passed the required tests.Conclusion MR Sim is high-precision and complex.To ensure its precise application in radiotherapy,the acceptance testing for an MR Sim should be meticulously designed and executed following the established guidelines and accounting for its unique performance characteristics.

Hyperbranched polymers (HBPs) have drawn great interest in the biomedical field on account of their special morphology, low viscosity, self-regulation, and facile preparation methods. Moreover, their large intramolecular cavities, high biocompatibility, biodegradability, and targeting properties render them very suitable for anti-tumor drug delivery. Recently, exploiting the specific characteristics of the tumor microenvironment, a range of multifunctional HBPs responsive to the tumor microenvironment have emerged. By further introducing various types of drugs through physical embedding or chemical coupling, the resulting HBPs based delivery systems have played a crucial part in improving drug stability, increasing effective drug concentration, decreasing drug toxicity and side effects, and enhancing anti-tumor effect. Here, based on different types of tumor microenvironment stimulation signals such as pH, redox, temperature, etc., we systematically review the preparation and response mechanism of HBPs, summarize the latest advances in drug delivery applications, and analyze the challenges and future research directions for such nanomaterials in biomedical clinical applications.

Objective:To explore the application value of scenario simulation teaching combined with two-way evaluation in standardized training of pediatric nursing.Methods:A total of 34 trainees who received standardized training of pediatric nursing in The First Affiliated Hospital of Air Force Medical University from March 2018 to March 2019 were selected as the control group, and another 42 trainees from April 2019 to July 2020 were selected as the study group. The control group used traditional teaching, and the study group used scenario simulation teaching combined with two-way evaluation. Theoretical examination and scenario simulation exercise examination were used to assess the theoretical knowledge and clinical practice ability of the trainees, and questionnaire survey was used to evaluate the satisfaction of the trainees with the teaching effect. SPSS 22.0 was used for t-test. Results:The scores of theoretical examination[(95.12±6.24) vs. (91.05±5.12)] and scenario simulation exercise examination (nursing practice skill operation ability, ability to combine theory and practice, clinical thinking and judgment ability, emergency handling ability, communication ability, humanistic care and professional learning ability, and work attitude) of the trainees in the study group were higher than those in the control group, and the differences were statistically significant ( P<0.05). The satisfaction evaluation of the trainees in the study group with the teaching effect was higher than that in the control group, and the difference was statistically significant ( P<0.001). Conclusion:Scenario simulation teaching combined with two-way evaluation can improve the theoretical knowledge, clinical practice ability, and teaching satisfaction of pediatric nursing trainees.

Objective:To investigate the value of serum miR-143 level combined with MRI in predicting the early response to concurrent chemoradiotherapy (CCRT) in cervical cancer.Methods:A total of 85 patients with pathologically confirmed cervical cancer underwent conventional MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The biopsy tissues and serum samples were collected. The differential expression of miRNA in the biopsy tissues was determined by microarray chip. The expression level of miR-143 in the serum samples was analyzed by qRT-PCR. All patients were divided into the non-residual and residual tumor groups according to post-treatment MRI. Pre-treatment clinical factors, MRI parameters and miR-143 between two groups were statistically analyzed by the univariate and multivariate analyses. The optimal thresholds and predictive performance for post-treatment incidence of residual tumors were estimated by drawing the ROC curve.Results:At one month after CCRT, there were 52 patients in the non-residual tumor group and 33 patients in the residual tumor group. In the residual tumor group, pre-treatment FIGO staging, apparent diffusion coefficient (ADC), D and V e were significantly higher (all P<0.05), whereas K trans value was significantly lower ( P<0.001) when compared to those in the non-residual tumor group. The miRNA array analysis showed that there were 16 miRNAs with differential expression levels between two groups (all P<0.05). Among them, the increase of miR-143 was the most significant in the residual tumor group. Compared with the residual tumor group, the expression level of serum miR-143 was significantly down-regulated in the non-residual tumor group ( P=0.002). Compared with the SiHa cells, the expression level of miR-143 in the SiHa-R cells was significantly up-regulated ( P<0.05). Multivariate analysis showed that only miR-143, D, K trans and V e were the independent prognostic factors. The combination of multi-parametric MRI and miR-143 exhibited the highest predictive performance (AUC=0.975), with a sensitivity of 84.8% and a specificity of 96.2%. Conclusion:The combination of multi-parametric MRI with miR-143 further improves the predictive performance for residual tumors after CCRT, which contributes to the personalized treatment of cervical cancer.

Objective:To improve the understanding of splenectomy for treating common variable immunodeficiency complicated with cytopenia.Methods:A case of common variable immunodeficiency complicated with cytopenia was reported, and the literature was reviewed.Results:The patient, female, 16 years old, was hospitalized for eight years due to thrombocytopenia; she manifested recurrent thrombocytopenia with leukopenia since adolescence. The patient was diagnosed with common variable immunodeficiency with repeated mild infections, splenomegaly, and significantly reduced plasma immunoglobulin levels. Additionally, splenectomy was performed with adequate immunoglobulin replacement therapy, and the pathology confirmed hypersplenism; her blood cell level returned to normal after surgery.Conclusions:Common variable immunodeficiency has various clinical manifestations and can be complicated with cytopenia. Under the premise of adequate immunoglobulin replacement therapy, splenectomy is a safe and effective treatment for common variable immunodeficiency in patients with recurrent cytopenia.

Objective:The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively.Methods:A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis.Results:The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively ( P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively ( P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion:The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

ABSTRACT OBJECTIVE：To establish a method for content determination of paclitaxel in malignant ascites of tumor patients. METHODS：LC-MS/MS method was adopted. Using vindoline as internal standard，the content of paclitaxel in ascites of tumor patients was determined. The separation was performed on Zorbax SB-C18 column with mobile phase consisted of aqueous solution （containing 0.1％ formic acid and 10 mmol/L ammonium acetate）-acetonitrile（40 ∶ 60，V/V）at the flow rate of 0.25 mL/min. the column temperature was 30 ℃，and sample size was 5 μL. The ion source was electrospray ion source，and the detection mode was multiple ion monitoring positive ion mode. MS parameters were set as following as dry gas temperature 350 ℃，dry gas flow rate 10 L/min，capillary voltage 4 000 V. Quantitative determination was operated in the multiple reaction monitoring（MRM）mode， with the ion transitions m/z 876.5→308.0 for paclitaxel and m/z 457.3→188.1 for the internal standard. The fragment voltage/ collision energy for paclitaxel and the internal standard were 250 V/30 eV，and 150 V/20 eV，respectively. RESULTS：The linear range of paclitaxel were 25-2 500 ng/mL（r2＝0.996 5，n＝7）. The lowest limit of quantitation was 25 ng/mL. RSDs of inter-day and intra-day precision tests were 0.61％ -3.62％（n＝5，3）. Accuracies were 95.34％ -98.76％（n＝5，3）. RSDs of extraction recovery were 3.19％-3.72％（n＝3）. CV of matrix effect were 1.52％-2.93％（n＝3）. RE of stability tests were lower than 3％（n＝ 3）. CONCLUSIONS：The method is simple，accurate and suitable for the content determination of paclitaxel in malignant ascites of tumor patients.

OBJECTIVE：To investiga te the effects of MEK/ERK pathway specific inhibitor PD 98059 combined with paclitaxel on the proliferation and apoptosis of human gastric signet ring cell carcinoma （SRCC）cells. METHODS ：Using human SRCC KATO Ⅲ cells as object ，CCK-8 assay was used to detect cell proliferation after treated with paclitaxel ，PD98059 and two drug combination for 48 h，and the proliferation rate was calculated. Flow cytometry ，Western blotting and Transwell assay were used to detect the cell proliferation ，the expression of apoptosis related protein （Cleaved-caspase-3）and cell migration after treated with paclitaxel，PD98059 and two drug combination for 48 or 24 h. RESULTS ：After treated with paclitaxel （1 μg/mL），PD98059（5， 20，40 μmol/L）and two drug combination （1 μg/mL+5，20，40 μmol/L），the proliferation rate of cells was increased significantly in administration groups ，and the combination groups were significantly higher than paclitaxel and PD 98059 alone groups （P＜ 0.05）. After treated with paclitaxel （1 μg/mL），PD98059（5，20，40 μmol/L）and two drug combination （1 μg/mL+40 μmol/L）， early and late apoptosis rate ，the protein expression of Cleaved-caspase- 3 were significantly increased in paclitaxel group and combination group ；combination group was significantly higher than paclitaxel and PD 98059 alone group （P＜0.05）. The number of migrated cells in administration groups were reduced significantly ，and the combination group was significantly lower than paclitaxel and PD 98059 alone group （P＜0.05）. CONCLUSIONS ：Paclitaxel and PD 98059 can inhibit the proliferation and migration of human SRCC KATO Ⅲ cells，paclitaxel can also promote the apoptosis and the expression of apoptosis related protein，which may be related to the inhibition of MEK/ERK pathway. The effect of the combination of the two drugs is better than paclitaxel or PD 98059 alone.