Objective: To analyze the drug resistance of multidrug-resistant organism (MDRO) among hospitalized children in a children's hospital in Hebei Province from 2019 to 2023, so as to provide the basis for the rational clinical application of antibacterial drugs. Methods: Specimens including sputum, blood, urine, pus, bronchoalveolar lavage fluid, secretions, pleural fluid, and peritoneal fluid of hospitalized children from January 2019 to December 2023 were collected. Pathogen identification and drug susceptibility tests were performed on methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Escherichia coli (ESBLs-EC), extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBLs-KP), carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Escherichia coli (CREC). The department distribution, specimen distribution, and drug resistance of MDROs were analyzed. Results: A total of 279 086 samples were submitted for testing, with 3 512 MDROs detected. Among these, MRSA and ESBLs-EC had relatively high detection rates of 35.76% and 41.50%, respectively. In the internal medicine pediatric patients, 1 869 MDROs were detected, accounting for 53.22%. The main departments were respiratory medicine, neonatology, and intensive care. In the surgical department, 1 643 MDROs were detected, accounting for 46.78%, with the main sources being general surgery and cardiac surgery. The highest numbers of MDROs were detected in sputum, pus, and urine samples, with 1 372, 527, and 494 isolates, representing 39.07%, 15.01%, and 14.07%, respectively. The resistance rates of MRSA to penicillin, oxacillin, and erythromycin were between 81.76% and 100.00%. ESBLs-EC and ESBLs-KP had a resistance rate of 100.00% to ceftriaxone. CRKP had a resistance rate of 100.00% to ampicillin/sulbactam and imipenem. CRAB had a resistance rate of 100.00% to cefoxitin, imipenem, and meropenem. CRPA had a resistance rate of 100.00% to ampicillin/sulbactam, ceftriaxone, cefoxitin, and imipenem. CREC had a resistance rate of 100.00% to imipenem. Conclusions In a children's hospital in Hebei Province, infections with MDROs among hospitalized pediatric patients are primarily caused by MRSA and ESBLs-EC. These infections are mainly distributed in the departments of respiratory medicine, neonatology, intensive care, general surgery, and cardiac surgery, with the highest detection rates in sputum, pus, and urine samples. Additionally, MRSA, ESBLs-EC, ESBLs-KP, CRKP, CRAB, CRPA, and CREC show high resistance rate to most antimicrobial agents.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn²⁺ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn²⁺, we constructed a TDN-MnO₂ complex and found that it displayed a much higher efficacy than TDN plus Mn²⁺ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO₂. These findings provide new therapeutic opportunities for cancer therapy.

Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these

The incidence of tinnitus is very high, which can affect the patient's attention, emotion and sleep, and even cause serious psychological distress and suicidal tendency. Currently, there is no uniform and objective method for tinnitus detection and therapy, and the mechanism of tinnitus is still unclear. In this study, we first collected the resting state electroencephalogram (EEG) data of tinnitus patients and healthy subjects. Then the power spectrum topology diagrams were compared of in the band of δ (0.5-3 Hz), θ (4-7 Hz), α (8-13 Hz), β (14-30 Hz) and γ (31-50 Hz) to explore the central mechanism of tinnitus. A total of 16 tinnitus patients and 16 healthy subjects were recruited to participate in the experiment. The results of resting state EEG experiments found that the spectrum power value of tinnitus patients was higher than that of healthy subjects in all concerned frequency bands. The
Attention ; Brain ; Electroencephalography ; Humans ; Parietal Lobe ; Tinnitus

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.

Objective: To explore the effects of miR-124-ROCK1 signal pathway in the damages of glomerular endothelial cells (GEnCs) induced by high glucose. Methods: Rat glomerular endothelial cells were cultured in different glucose concentrations: normal control group (NG: 5.5 mmol/L), high glucose group (HG: 30.0 mmol/L), and cells were treated with ROCK1 inhibitor Y27632, miR-124-3p mimic, miR-124-3p inhibitor. The expressions of ROCK1 activity, cell apotosis and tight junction proteins were detected by Western blot. The cell tight junction protein ZO-1 in those groups were assessed by laser scanning confocal microscope. Results: High glucose significantly decreased miR-124 expression (P<0.01), ROCK1 activity (P-MYPT1/MYPT1), and cell apoptosis (Cleaved-Caspase3/pro-Caspase3) were found increased while the tight junction proteins ZO-1and Occludin were found decreased in these cells (P<0.05 all P<0.01), However, when pretreated cells with ROCK1 inhibitor Y27632, these injuries were significantly reversed. In cells transfected with miR-124-3p mimic, p-MYPT1/MYPT1 was decreased. p-MYPT1/MYPT1 was however increased in cells transfected with miR-124-3p inhibitor (P<0.05), indicating that miR-124 could directly inhibit ROCK1 activity. The increased ROCK1 activity and apoptosis, as well as the decreased tight junction proteins induced by high glucose were significantly suppressed as miR-124-3p mimic transfected in GEnCs. Conclusions According to our experiments, high glucose suppressed miR-124 in glomerular endothelial cells, consequenctly activating ROCK1 activity to damage endothelial cells. MiR-124 overexpression could ameliorate these damages induced by high glucose, suggesting that miR-124 might be a new therapeutic target to prevent glomerular endothelial cells injuries in diabetic nephropathy.

Objective:To study the antimicrobial properties of CaO/ZnO core-shell nanoparticles.Methods:The CaO/ZnO core-shell nanoparticles were prepared via precipitation method.The pH and calcium ion release from the samples which composed of eugenol and nanoparticles were examined respectively.The form of the particles was observed under electron microscope,the ions were analysed by inductively coupled plasma(ICP).The antibacterial activities against Streptococcus mutans,Enterococcus faecalis,Escherichia coli and Staphylococcus aureus were evaluated by agar diffusion test (ADT).Results:CaO/ZnO core-shell nanoparticles were spherical with core-shell structure and with the diameter of 80-90 nm.The calcium ion release and pH were gradually increasing from the nanoparticles in PBS.The antibacterial activity of CaO/ZnO core-shell nanoparticles-eugenol was significantly greater than that of iRoot SP and zinc oxide-eugenol sealer(P<0.01).Conclusion:CaO/ZnO core-shell nanoparticles possess antibacterial activity.

Objective By detecting vascular cysteine-rich 61(Cyr61) related factor,connective tissue growth factor (CTGF),vascular endothelial growth factor (VEGF) and CD105 markers of microvascular density (MVD) of muscle tissue in patients with PM/DM,the role and significance of the expression of Cyr61,CTGF,VEGF and CD105 in the process of vascular lesions of dermatomyosits (DM) and polymyosits (PM) were discussed.Methods The expression of Cyr61,CTGF,VEGF and CD105 markers of micro vascular density (MVD) were detected in 10 cases of DM,10 cases of PM and 20 controls by using immunohistochemical Envision two step method.Data were analyzed using Statistical Product and Service Solutions (SPSS) statistical software.Fisher's exact probability analysis and Spearman correlation analysis were conducted.Results Compared with the control group,Cyr61,CTGF,VEGF positive expression rate in muscle tissue of patients with DM and PM group were significantly different (P＜0.01),the positive expression rates of Cyr61,CTGF,VEGF in DM group and PM group were 90％,70％,90％,80％,80％,70％,and the control group (5％,10％,5％) respectively.In the muscle tissue of patients with DM and PM group,CD105 markers of capillaries could be seen,and MVD in DM and PM group were higher than that in the control group,the difference was statistically significant (F=8.103,P=0.001).Cyr61,CTGF and VEGF protein expression levels in muscle tissueof patients with DM and PM were positively correlated with MVD.Conclusion The muscle tissue of PM/DMpatients may have new blood vessels formation.Cyr61,CTGF,VEGF may be involved in the formation of newblood vessels in the PM/DM muscle tissue.The results of this study suggest that microvascular lesion plays animportant role in the immune pathogenesis of inflammatory myopathy such as PM/DM.