Objective To use superparamagnetic iron oxide nanoparticles(SPIONs)to label chimeric antigen receptor(CAR)T cells targeting carcinoembryonic antigen(CEA),and perform magnetic resonance imaging(MRI)to real time trace CEA CAR-T cells in vivo.Methods Appropriate amount of ferumoxytol,heparin sodium and protamine sulfate were mixed at high(ferumoxytol 100 μg/mL,heparin sodium 4 IU/mL,protamine sulfate 120 μg/mL),medium(ferumoxytol 50 μg/mL,heparin sodium 2 IU/mL,protamine sulfate 60 μg/mL),and low(ferumoxytol 25 μg/mL,heparin sodium 1 IU/mL,protamine sulfate 30 μg/mL)concentrations to form a SPIONs complex ferumoxytol/heparin/protamine(FHP),and then co-incubated with CEA CAR-T cells for cell labeling.The biocompatibility of FHP was detected by CCK-8 assay,EdU assay and flow cytometry.The uptake of FHP was detected by Prussian blue staining,and SPIONs content in the cells was quantitatively detected by inductively coupled plasma-mass spectrometry(ICP-MS).Flow cytometry was used to detect the lytic effect of FHP-labeled CEA CAR-T cells on tumor cells,and MRI was employed to scan FHP-labeled CEA CAR-T cells.Results FHP at high,medium,and low concentrations had no significant effect on the activity of CEA CAR-T cells,with cell activity above 100％determined by CCK-8 assay.DNA proliferation was above 94.3％in EdU assays.Prussian blue staining showed that CEA CAR-T cells could take FHP up,with the uptake increased with the increment of FHP concentration.ICP-MS showed that the intracellular Fe content was 440.23±189.36 ng/mL.Tumor cell killing experiment showed that FHP-labeled CEA CAR-T cells had excellent killing capability against tumor cells.MRI scans indicated that T2WI signals of FHP-labeled CEA CAR-T cells were significantly reduced with increasing FHP concentration(P＜0.01).Conclusion SPIONs complex FHP shows good biocompatibility and can effectively label CEA CAR-T cells.SPIONs complex FHP can be used as a magnetic marker for CEA CAR-T cells and a feasible MRI tracer for clinical application.

Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring.Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group,and the offspring mice were fed normally for 16 weeks after the mother gave birth.Western blot and RT-qPCR were used to detect the expression and transcription of related proteins,and immunofluorescence and im-munohistochemical staining were used for pathological analysis.Results Compared with the offspring of maternal nor-mal diet during pregnancy,the expressions of vascular inflammatory factors,macrophage infiltration,monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet(OHF)during pregnancy(P＜0.05).Vas-cular endothelial nitric oxide synthase(eNOS)activity,nitric oxide(NO)level were dramatically reduced(P＜0.05).Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin(α-SMA)in OHF.Western blot analysis further confirmed the results,which showed that maternal high fat diet reduced vascular endothelial-cadherin(VE-cadherin)and CD31 and increased α-SMA and Vimentin in the offspring(P＜0.05).The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta(TGF-β)/Smad signaling in endothelium(P＜0.05).Moreover,the maternal high fat diet reduced Kruppel-like factor 2(KLF2)expression by 76％in mRNA level and 59％in protein level(P＜0.05).Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta.The results provide a clue for prevention of vascular disease in early stage.

Red blood cells(RBCs)are the primary mediators of oxygen transport in the human body,and their function is mainly achieved through conformational changes of hemoglobin(Hb).Hb is a tetramer composed of four subunits,with HbA being the predominant Hb in healthy adults,existing in two forms:tense state(T state)and relaxed state(R state).Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid,carbon dioxide,protons,and chloride ions,while exogenous regulators include inositol hexaphosphate,inositol tripyrophosphate,benzabate,urea derivative L35,and vanillin,each with different mechanisms of action.The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

Objective:To explore the relationships among 4 primary indicators in the performance assessment and evaluation system of tertiary public hospitals.Methods:A questionnaire survey was employed to collect data on healthcare professionals'perceptions of the rationality of performance evaluation indicators.Structural equation modeling(SEM)and Amos 21.0 Statistical Software were utilized for data analysis,with the mediation effects tested using the Bootstrap method.Results:A total of 826 valid questionnaires were obtained.Medical quality,operational efficiency,and sustainable development had a positive impact on satisfaction.Operational efficiency and sustainable development played a chain-mediated role in the process of medical quality influencing satisfaction evaluation,namely"medical quality → operational efficiency → sustainable development → satisfaction".Conclusion:It helps to flexibly apply and deepen the integration of knowledge in the field of enterprise management into the field of hospital management,helps hospitals to scientifically formulate internal performance evaluation programs under the premise of limited resources,and provides new ideas for the country to optimize the performance appraisal index system of tertiary public hospitals.

Objective: We aimed to predict the possible mechanism of obsessive-compulsive disorder (OCD) by integrating and analyzing mRNA sequencing results from two datasets and to provide direction for future studies into the pathogenesis of OCD. Methods: Two OCD datasets, GSE78104 and GSE60190, were obtained, and the intersection of the two gene sets with differential expression in OCD samples was selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and Gene Ontology (GO) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online analysis website for the genes at the intersection, and the data were mapped using http://www.bioinformatics.com.cn. After genes with p≤0.05 had been screened out, protein-protein interaction (PPI) interaction analysis was conducted using Metascape to screen the key Molecular Complex Detection (MCODE) genes. MCODE genes were then enriched using the KEGG signaling pathway and GO classification. Results: A total of 3,449 differentially expressed genes (DEGs) were obtained from the GSE78104 and GSE60190 datasets. KEGG, GO, and Gene Set Enrichment Analysis analyses of DEGs showed that the onset of OCD was related to oxidative phosphorylation and other metabolic processes, which may have a similar pathogenesis to other neurodegenerative diseases. Single-gene PPI analysis of SAPAP3 revealed that the mechanism by which SAPAP3 knockout induces OCD may also be caused by affecting oxidative phosphorylation. Conclusion The mechanism of SAPAP3 knockout-induced OCD in mice may be due to the oxidative phosphorylation process in the body. Future studies on the neural circuit mechanism of OCD should be conducted.

Monoclonal gammopathy of undetermined significance combined with renal damage is named monoclonal gammopathy of renal significance. There are few reports about IgA vasculitis in patients with monoclonal gammopathy of undetermined significance. Here, we report a case of monoclonal gammopathy of renal significance, who had manifestations of IgA vasculitis, including purpura, gastrointestinal bleeding and joint pain. The patient had elevated serum creatinine levels, prompting further investigation through immunofixation electrophoresis and bone marrow aspiration biopsy. Immunofixation electrophoresis showed IgA-λ-type monoclonal immunoglobulin, while the bone marrow aspiration biopsy suggested plasmacytosis. Kidney biopsy indicated membranous hyperplastic glomerulonephritis, light and heavy chain deposition, IgA-λ. The patient was diagnosed with monoclonal gammopathy of renal significance. In light of the elevated serum creatinine, the patient was treated with chemotherapy regimen (bortezomib +cyclophosphamide +dexamethasone). After chemotherapy, there was no significant improvement in the patient's renal function. Subsequently, the patient experienced abdominal pain, skin purpura, joint pain and severe gastrointestinal bleeding. Gastroenteroscopy did not find the exact bleeding position. Angiography revealed hyperplasia of left jejunal artery. Surgical operation found that the bleeding site was located between the jejunum and ileum, where scattered hemorrhagic spots and multiple ulcers were present on the surface of the small intestine, with the deepest ulcers reaching the serosal layer. And the damaged intestine was removed during the operation. Intestinal pathology showed multiple intestinal submucosal arteritis, rusulting in intestinal wall necrosis and multiple ulcers. Considering intestinal lesions as gastrointestinal involvement of IgA vasculitis, methylprednisolone was used continually after the operation, and the patient's condition was improved. However, after half a year, the patient suffered a severe respiratory infection and experienced a recurrence of serious gastrointestinal bleeding. It was considered that the infection triggered the activity of IgA vasculitis, accompanied by gastrointestinal involvement. Finally, the patient died from gastrointestinal bleeding. The present case represented a patient with monoclonal gammopathy of renal significance and IgA vasculitis, prominently presenting with renal insufficiency and severe gastrointestinal bleeding, making the diagnosis and treatment process complex. Patients with IgA monoclonal gammopathy who presented with abdominal pain, purpura, and arthralgia should be vigilant for the possibility of concomitant IgA vasculitis. The treatment of cases with IgA vasculitis combined with monoclonal gammopathy of renal significance was rather challenging. Plasma cell targeting therapy might be an effective regimen for IgA vasculitis with monoclonal gammopathy. However, patients with poor renal response to the treatment indicated poor prognosis.
Humans ; Cyclophosphamide/administration & dosage* ; Gastrointestinal Hemorrhage/etiology* ; IgA Vasculitis/complications* ; Immunoglobulin A ; Intestine, Small/pathology* ; Kidney/pathology* ; Kidney Diseases/pathology* ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Necrosis ; Paraproteinemias/complications* ; Vasculitis/etiology*

【Objective】 To investigate the relationship between maternal oral health behavior during pregnancy and premature birth. 【Methods】 A total of 248 preterm and 700 non-preterm pregnant women who delivered in Northwest Women’s and Children’s Hospital in Shaanxi Province from January to December 2022 were included in case group and control group, respectively. General demographic characteristics and oral health behavior during pregnancy were collected by questionnaires, and the oral health impact profile-14 (OHIP-14) was used to assess the oral health related life quality of pregnant women. Logistic regression model was used to analyze the relationship between maternal oral health behavior during pregnancy and premature birth. 【Results】 During pregnancy, maternal frequent eating after brushing teeth (OR=1.62, 95% CI: 1.03-2.57), unused fluoride toothpaste (OR=2.03, 95%CI: 1.25-3.05), late visit to the doctor for oral discomfort (OR=1.41, 95%CI: 1.02-1.96), brushing teeth less than twice one day (OR=1.77, 95%CI: 1.13-2.78) or less than 3 minutes each time (OR=1.52, 95%CI: 1.09-2.11), and elevated OHIP-14 score (OR=1.07, 95%CI: 1.04-1.10) increased the risk of premature birth. 【Conclusion】 Poor oral health behavior during pregnancy may increase the risk of premature birth. Therefore, more efforts should be made to publicize oral health knowledge and guide pregnant women to establish good oral health habits so as to improve oral health and promote maternal and child health.

Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.

Objective:To elucidate the molecular mechanism(s) by which methyl salicylate enhances the skin de-livery of herbal ingredients with diverse lipophilicity.Methods:The toxicity of methyl salicylate on skin cell lines was evaluated using the MTT assay.The Franz diffusion cell method was used to measure the permeability enhancing activities of methyl salicylate for five herbal ingredients with a range of lipophilicities.The interaction between methyl salicylate and the stratum corneum (SC) was observed by using an infrared spectroscopy technique.Moreover,the solu-bilities and SC-vehicle partition coefficient were determined to monitor the impact of methyl salicylate on the drug thermodynamic activities and partition into the SC layer,respectively.Results:Compared with azone (1-dodecylazacycloheptan-2-one),methyl salicylate showed lower toxicity to skin cells in terms of the ICso values.The in vitro skin permeation studies showed that methyl salicylate could greatly improve the cumulative amounts or steady state flux of the selected model drugs with the exception of osthole,which indicated that methyl salicylate was prone to promote the skin delivery of hydrophilic drugs.The Fourier transform infrared spectroscopy studies revealed that methyl salicylate mainly interacted with SC lipids,leading to the disruption of the orderly arrangement of the SC.In addition,methyl salicylate had no obvious effect on the drug thermodynamic activity and partition into the SC.Conclusion:Methyl salicylate could effectively promote the skin delivery of relatively hydrophilic in-gredients in externally used traditional Chinese medicines (TCM) without obvious cytotoxicity.

AIM: The main chemical components of Yufang Fangji II (Hubei Fang) of COVID-19 were studied systematically and combined with network pharmacology to provide a reference for the study of its effective substances. METHODS: Ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) was applied to identify the absorbed components of the prescription in rat plasma. TCMSP database and Swiss Target Prediction data platform were used to predict the target of the identified blood components, and network visualization software Cytoscape 3.7.2 was used draw the association network diagram, and GO enrichment analysis and KEGG pathway enrichment analysis were conducted for the key targets. With the help of CB-Dock online molecular docking platform, the molecular docking of key targets and blood entering compounds was carried out, and the docking combination with good affinity value was displayed by ligplot software to verify the preventive effect of Yufang Fangji II on COVID-19. RESULTS: A total of 52 chemical components identified in the prescription, in which 13 components were absorbed in the rat plasma as the prototype, and they were from Astragalus membranaceus, Atractylodes macrocephala, Saposhnikoviae Radix, Lonicerae Japonicae Flos, and Citri Reticulatae Pericarpium, respectively. These compounds were recognized to act on 17 core targets, including mapk3, TNF and other targets related to inflammation, MPO and other targets related to oxidative stress, VEGFR, KDR and other targets related to vascular endothelium. The results of molecular docking showed that the absorbed components had good binding activity with the key targets. CONCLUSION: Compounds in Yufang Fangji II are involved in regulating inflammation, oxidative stress, vascular and cellular physiological activities, which have preventive effects on COVID-19 through regulating IL-17, PI3K Akt, MAPK and other pathways.