Objective To develop engineered bacterial membrane biomimetic nanoparticles,Angiopep-2 E.coli membrane(ANG-2 EM)@PDA-PEI-CpG(ANG-2 EM@PPC),for efficient targeted drug delivery in the treatment of glioma,and to provide theoretical and technical support for targeted glioma therapy.Methods The expression of inaX-N-angiopep-2 engineered bacteria was constructed in the laboratory,and ANG-2 EM was obtained through lysozyme treatment and ultrafiltration centrifugation.ANG-2 EM@PPC was prepared by ultrasonication of bacterial membranes.Western blotting,agarose gel electrophoresis,and transmission electron microscopy(TEM)were used to verify the preparation.Particle size and Zeta potential were measured to investigate the stability of ANG-2 EM@PPC.Regarding cell experiments,CCK-8 assay was performed to determine the effect of ANG-2 EM@PPC on the survival rate of neutrophils.A flow chamber model was designed and constructed,and the uptake efficiency of neutrophils was measured by flow cytometry to investigate the hitchhiking efficiency of ANG 2 EM@PPC on neutrophils in inflammatory environment.Neutrophil death patterns were characterized by fluorescence microscopy,and flow cytometry and Western blotting were performed to examine neutrophil apoptotic bodies and the proportion of apoptotic bodies produced.Regarding animal experiments,a mouse model of in situ glioma was established and the inflammatory environment of tumor tissue was verified.The tumor model mice were divided into three groups,including DiR group,EM@PPC group,and ANG-2 EM@PPC group(all n=3),which were injected with DiR,ANG-2 EM@PDA-PEI-CpG,and EM@PDA-PEI-CpG via the tail vein,respectively(all at 10 mg/kg).Fluorescence images of organs and the brain were used to examine the distribution of the three formulations in vivo and in the brain.The tumor model mice were further divided into PBS group,PDA group,PC group,PPC group,EM@PPC group,and ANG-2 EM@PPC group(all n=4),which were injected with PBS,PDA,PC,PPC,EM@PPC,and ANG-2 EM@PPC injected via the tail vein,respectively(all at 10 mg/kg).Imaging was performed in vivo to observe tumor regression,and the survival rate and body mass of mice were measured to evaluate in vivo pharmacodynamics.TUNEL staining(brain tissue)and HE staining(brain,heart,liver,spleen,lung and kidney tissues)were performed to evaluate the therapeutic effect.Results The results of TEM showed successful preparation of engineered bacterial membrane biomimetic nanoparticles,with PPC exhibiting a distinct shell-core structure and a shell thickness of about 8.2 nm.Due to the coating of ANG-2 EM,the shell thickness of ANG-2 EM@PPC increased to about 9.6 nm,with a clear bacterial membrane layer on the surface.Stability was maintained for at least one week.ANG-2 EM@PPC had no significant effect on the activity of neutrophils according to the findings from the CCK-8 assay.Flow cytometry showed that ANG-2 EM@PPC uptake is enhanced in activated neutrophils and hitchhiking on neutrophils was more efficient in the stationary state than that in the flowing condition.Compared with the EM@PPC group,the neutrophil hitchhiking ability of the ANG-2 EM@PPC group was enhanced(uptake efficiency 24.9%vs.31.1%).Fluorescence microscopy showed that ANG-2 EM@PPC changed the death pathway of neutrophils from neutrophil extracellular traps-osis(NETosis)to apoptosis.Western blot confirmed the production of neutrophil apoptotic bodies,and flow cytometry showed that the production rate was as high as 77.7%.Animal experiments showed that there was no significant difference in the distribution of engineered bacterial membrane biomimetic nanoparticles in the organs(heart,liver,spleen,lungs,and kidney)in the DiR group,the EM@PPC gropu,and the ANG-2 EM@PPC group(P＞0.05),but there was higher distribution in the brain tissue in EM@PPC and ANG-2 EM@PPC groups compared to the DiR group(P＜0.05).Engineered bacterial membrane biomimetic nanoparticles crossed the blood-brain barrier(BBB),and exhibited high affinity to and internalization by neutrophils located in brain tumors.Compared with PBS,PDA,PC,and PPC groups,the survival rate and body mass of mice in the EM@PPC group were improved,tumor fluorescence intensity was weakened,and apoptotic cells were increased.These trends were even more prominent in the ANG-2 EM@PPC group.No abnormality was found in the HE staining of any group.Conclusion An ANG-2 EM@PPC nanodelivery system with inflammation response characteristics was successfully prepared,capable of crossing BBB and targeting the tumor inflammatory microenvironment to improve the anti-glioma efficacy.This study provides a new drug delivery strategy for glioma treatment and offers a new idea for targeted drug delivery in the non-invasive inflammatory microenvironments in other central nervous system diseases.

Objective:To explore the status quo and influencing factors of anxiety among caregivers of children with cancer during chemotherapy to provide a reference for clinical intervention.Methods:In this cross-sectional study, 133 caregivers of children with cancer during chemotherapy admitted at the First Affiliated Hospital of Zhengzhou University between May and August 2020 were selected by convenient sampling and investigated with the General Information Questionnaire, Generalized Anxiety Disorder-7 (GAD-7) , and Chinese version of Cognitive Fusion Questionnaire (CFQ) . In this study, a total of 133 questionnaires were distributed and 124 valid ones were returned, accounting for an effective response rate of 93.2%.Results:The GAD-7 score of the 124 caregivers was 10.50 (6.00, 15.75) ; the incidence of anxiety was 84.68% (105/124) ; and the Chinese version of CFQ score was 42.00 (32.00, 50.00) . There was a positive correlation between the GAD-7 and CFQ scores ( r=0.639, P<0.01) . Binary logistic regression analysis showed that cognitive fusion was a risk factor for anxiety among caregivers of children with cancer during chemotherapy ( P<0.01) . Conclusions:The anxiety and cognitive fusion levels among caregivers of children with cancer during chemotherapy are relatively high and positively correlated with each other. Targeted interventions should be provided in clinical practice for the cognitive fusion of caregivers of children with cancer during chemotherapy to reduce their anxiety and improve the quality of care for children.

Objective:To explore the effect of the training model based on the National Telemedicine Center in the technical training of children's implantable venous access port.Methods:Using the convenience sampling, 42 nurses who participated in the technical training of children's implantable venous access port in the First Affiliated Hospital of Zhengzhou University from May 2019 to December 2019 were selected as the study group. A total of 36 nurses who participated in the technical training of children's implantable venous access port in the First Affiliated Hospital of Zhengzhou University from December 2018 to March 2019 were retrospectively selected as the control group. The control group received the traditional training, and the study group implemented the training model based on the National Telemedicine Center. The theoretical assessment, operational assessment and training satisfaction were compared between the two groups before and after training.Results:After training, the theoretical assessment, operational assessment and training satisfaction scores of the study group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The training model based on the National Telemedicine Center in the technical training of children's implantable venous access port can enhance the professional knowledge and practical skills of nurses and improve the training satisfaction.

ObjectiveTo explore the correlation between post-traumatic stress disorder(PTSD) and emotional regulation in the parents whose children have acute lymphoblastic leukemia(ALL). MethodsBy convenient sampling method, a total of 233 parents whose children had ALL were selected in the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017, and the levels of PTSD and emotional regulation were evaluated by The PTSD Checklist-Civilian Version (PCL-C) and Emotion Regulation Questionnaire(ERQ). A total of 233 questionnaires were distributed and 233 valid ones were retrieved, yielding an effective recovery rate of 100%. ResultsIn this study, the participants got (35.82±4.93) points for PCL-C, among which the highest average item score was (2.29±0.36) points for "Avoid/Numb"; the score of "cognitive reappraisal" and"expressive suppression" were (4.27±0.64) and (4.35±0.60) points in ERQ. Pearson correlation analysis showed that the total score and each dimension score in PCL-C were negatively correlated with cognitive reappraisal (P＜0.05), and were positively correlated with expressive suppression (P＜0.05). Multivariate linear regression analysis showed that cognitive reappraisal and expressive suppression were the influencing factors for PTSD of the parents with ALL children (P＜0.05). ConclusionsALL children's parents have serious PTSD and tend to choose the emotional regulation way of expressive suppression. There is correlation between the degree of PTSD in ALL children's parents and their emotional regulating ability, therefore, nursing staff should assist them in the improvement of their emotional regulation ability to reduce the level of PTSD.

Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Objective To validate the effect of Renji acute kidney injury score (RAKIS) on predicting patients with acute kidney injury (AKI) after cardiac surgeries,and make comparison with Cleveland score,simplified renal index (SRI) and acute kidney injury following cardiac surgery (AKICS).Methods Patients undergoing open heart surgery from 2008/01/01 to 2010/10/31 in Renji hospital were enrolled,and their scores of those four scoring models were calculated.AKI patients were diagnosed by KDIGO,and those scores of AKI patients and non-AKI patients were compared.Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to decide the predictive values of those models.Results A total of 1126 patients were chosen in this cohort,with the average age of (58.43±14.88) years (rang from 18 to 88).The male to female ratio was 1.47:1.And 355(31.5％) patients were developed AKI.AKI stage Ⅰ,Ⅱ and Ⅲ were 65.4％,23.7％ and 11.0％ respectively.RAKIS was significantly higher in AKI patients than in non-AKI patients (17.5 vs 9.0,P ＜ 0.001).The AUCs of RAKIS to predict AKI,AKI Ⅱ-Ⅲ stages,renal replacement therapy (RRT)and in-hospital death were 0.818,0.819,0.800 and 0.784 respectively.The AUCs of Cleveland score and SRI were 0.659 to 0.710,lower than those of RAKIS and AKICS.AKICS had lower value for predicting AKI and AKI Ⅱ-Ⅲ stages (AUC 0.766 and 0.793),but good value in predicting RRT and inhospital death after surgery (AUC 0.804 and 0.835) as compared with RAKIS.Conclusions RAKIS is valid and accurate in the discrimination of KDIGO defined AKI patients,while for predicting the composite end point,AKICS may be more useful.

Objective To investigate the prevalence and cardiovascular risk factors of silent brain infarct (SBI) in Shunyi Cohort.Methods This study was based on the population based Shunyi Study in China.One thousand and twenty-seven stroke-free participants older than 35 years,who completed cerebral MRI,were included.Cardiovascular risk factors were assessed by interview,physical examination and blood sample tests.SBI was evaluated on 3D-T1WI,T2WI and FLAIR sequences.Associations between risk factors and SBI were analyzed by Logistic regression and adjusted for age,sex,and relevant confounders.Results One thousand and twenty-seven participants,aged (55.9 ± 9.4) years,37.7％ male,were assessed.One hundred sixty-four participants(16.0％) had SBI on MRI.The prevalence of SBI increased by age (every 10 years,OR=2.12,95％ CI 1.74-2.58,P＜0.01).Hypertension(OR =2.67,95％ CI 1.77-4.04,P＜0.01),diabetes(OR=2.48,95％ CI 1.64-3.76,P＜0.01) and smoking(OR=1.98,95％ CI 1.08-3.62,P =0.028) were significantly associated with SBI.Conclusions The prevalence of SBI in this Chinese population is 16.0％,which increases with age.Hypertension,diabetes and smoking are associated with SBI.

Objective To determine the relationship between serum soluble Klotho (sKL) level and adverse outcome in maintenance hemodialysis (MHD) patients.Methods One hundred and twenty nine cases of MHD patients were collected prospectively.Serum sKL was detected by ELISA.Abdomen lateral plain was used as a criterion to determine the abdominal aortic calcification.The abdominal aortic calcification score (AAC) was calculated.Cox regression analysis was used to determine the risk factor of cardiovascular death (CVD) in MHD patients.Kaplan-Meier showed the relationship between sKL and CVD in MHD patients.Results There were 27 cases (20.9％) of allcause death and 19 cases (14.7％) of cardiovascular death.The median sKL was 612.6(379.2-816.6) nig/L,and log[iPTH] was an independent factor of sKL concentration.Low sKL had high AAC and CVD death rate.Kaplan-Meier method showed that the all-cause death rate was similar between two groups,and CVD death rate increased significantly in low sKL patients (P=0.036).Cox regression indicated that lower sKL level was associated with high CVD death rate [OR=0.352,95％CI(0.127-0.977),P=0.045].After adjustment for the general condition,biochemical indicators,the relationship still existed [OR=0.331,95％ CI (0.117-0.933),P=0.037].In no or mild vascular calcification patients (AAC ≤4),compared with high sKL patients,low sKL patients had no significant difference rate in all-cause mortality.The CVD mortality was significantly higher in high sKL (P=0.035) compared with low sKL.In severe calcification group (AAC ＞ 4),all-cause death and CVD death rates were similar between different sKL groups (P=0.991 and 0.522,respectively).Conclusions Lower sKL has the high CVD death rate and sKL level decreasing is an independent risk factor for CVD death in MHD patients.The lower sKL concentration in MHD patients with no or mild calcification may predict CVD mortality.This study suggests that sKL levels may be helpful in predicting the outcome of patients with MHD.

Objective To investigate the relationship between serum phosphorus variability and mortality in maintenance hemodialysis (MHD) patients. Methods A total of 502 MHD cases from Renji hospital hemodialysis center were registered in Shanghai Registry Network from January 2007 to April 2015. They were recruited with general information, laboratory results and outcomes. According to their median of coefficient of variation (CV) of blood phosphorus, the patients were divided into high variation group (CV≥0.226 mmol/L) and low variation group (CV<0.226 mmol/L). The relationship of serum phosphorus CV with all?cause mortality and cardiovascular disease mortality was assessed respectively. Results The average age was (63.9±14.6) years, the median dialysis age was 82.0 (43.0, 139.0) months, 118 patients (23.5%) died for all cause and 64 patients (12.7%) died for cardiovascular disease. Compared with patients in low phosphorus variation group, patients had a higher all?cause mortality in high phosphorus variation group (27.7% vs 19.3%, P=0.028). Higher cardiovascular disease mortality was observed in high variation group as well, but this difference was no statistical significant (15.4% vs 10.0%, P=0.082). COX regression analysis showed that >60 years of age (HR=2.762, 95%CI 1.707?4.468, P<0.001), low hemoglobin (HR=0.466, 95%CI 0.317?0.686, P<0.001), low albumin (HR=0.555, 95%CI 0.366?0.840, P=0.005), high CV of phosphorus (HR=1.479, 95%CI 1.023 ? 2.139, P=0.037) were independent risk factors for all ? cause mortality. Moreover, >60 years of age (HR=2.666, 95%CI 1.469?4.837, P=0.001), low hemoglobin (HR=0.480, 95%CI 0.238?0.801, P=0.005), and high CV of phosphorus (HR=1.655, 95%CI 1.003?2.729, P=0.049) were independent risk factors for cardiovascular disease mortality. There was no significant statistical difference between patients phosphorus on target and patients phosphorus below target in all?cause disease mortality (P=0.065) and cardiovascular disease mortality (P=0.425). High variation group whose phosphorus on target had higher all?cause mortality and cardiovascular disease mortality than those in low variation group (29.2% vs 16.9%, P=0.047; 15.0% vs 6.0%, P=0.033). Kaplan?Meier method showed that patients with high phosphorus variation had higher all?cause (P=0.023) and cardiovascular disease mortality (P=0.047) than patients with low phosphorus variation. Conclusions The high CV of phosphorus is independently correlated with all?cause and cardiovascular disease mortality. Patients with standard ? reaching phosphorus in the low variation group have a lower mortality. A serum phosphorus level sustainably reaching the standard may improve the survival in MHD patients.