OBJECTIVE To synthesize a polymer PEI-ss-PEG2000-DSPE containing disulfide bond and to prepare as cationic micelle(P-ss-PD) based on branched polyethyleneimine(PEI). To investigate the ability of P-ss-PD micelle to reduce cytotoxicity and improve the transfection efficiency of antisense oligonucleotide(ASO) in human breast cancer cell lines, and to study the anti-tumor effect of P-ss-PD micelle in nude mice. METHODS PEI-ss-PEG2000-DSPE was synthesized by grafting PEG2000-DSPE onto branched PEI with disulfide bond as a connecting arm. P-ss-PD micelle was prepared by ethanol injection method and P-ss-PD/ASO nanocomplex was obtained by combining P-ss-PD micelle with ASO. The particle size and zeta potential of P-ss-PD/ASO nanocomplex at various mass ratios were determined by laser particle size analyzer. Agarose gel retardation assay was used to investigate the binding degree of P-ss-PD/ASO nanocomplex and determine the optimal mass ratio. At the same time, the reduction responsive ability of P-ss-PD micelle was investigated. The cytotoxicity of P-ss-PD micelle was detected by CCK8 kit. The transfection efficiency of P-ss-PD micelle was investigated by flow cytometry and high content cell imaging analysis system in MDA-MB-231 cells. The anti-tumor effect of P-ss-PD micelle was investigated by tumor-bearing nude mice models. RESULTS When the mass ratio was 300∶1, the particle size of P-ss-PD/ASO nanocomplex was the smallest and had a good stability. The average particle size was (58.90 ± 4.08)nm, the average zeta potential was (16.80 ± 1.23)mV, and the morphology was uniform spherical. P-ss-PD/ASO nanocomplex had the reduction responsive ability and could release ASO under highly reductive conditions.In vitro, compared with unmodified branched PEI, the cytotoxicity of P-ss-PD micelle was significantly reduced and the transfection efficiency was significantly increased.In vivo, the tumor growth inhibition rate of P-ss-PD/ASO nanocomplex in tumor-bearing nude mice was more than 50%. CONCLUSION The P-ss-PD micelle prepared in this study is a kind of low toxicity and high transfection efficiency non-viral vector, which has the characteristics of reduction responsive releasing, and shows a promising application in ASO drug delivery.

Objective:To describe the epidemiological characteristics of respiratory syncytial virus (RSV) infection in preschool children and explore the risk factors for severe pneumonia.Methods:Epidemiological data of 279 preschool children with RSV infection were investigated. The children were screened for severe pneumonia and separated into ordinary and severe types. General data and laboratory test data from both groups were compared, and binary logistic regression model analysis was applied to determine the risk factors for severe pneumonia.Results:Preschool children with RSV infection were mostly male (63.08%), <6 months old (65.95%) and had poor living environment (53.05%), with main symptoms of cough (91.04%) and wheezing (69.18%), the lung auscultation was mainly characterized by wheezing (86.74%), and imaging findings were mainly patchy shadows (76.34%), the onset season was concentrated in autumn (31.18%) and winter (43.37%). The detection rate of severe pneumonia in 279 pediatric patients was 20.27% (56/279). The proportions of onset season being autumn or winter, low birth weight infants, history of respiratory infections within 3 months, delayed treatment, neutrophils count <10×10 9/L, C-reactive protein≥10 mg/L, procalcitonin≥1.5 ng/mL, albumin<30 g/L, CD4 + /CD8 + <1.2 in the severe types were higher than those in the normal types ( P<0.05). Logistic regression analysis showed that the onset season was autumn or winter ( OR=2.316, 95% CI: 1.235-4.345), low birth weight infants ( OR=2.679, 95% CI: 1.442-4.977), history of respiratory infections within 3 months ( OR=2.815, 95% CI: 1.539-5.148), delayed treatment ( OR=2.869, 95% CI: 1.581-5.206), low albumin<30 g/L ( OR=2.756, 95% CI: 1.495-5.080), and low CD4 + /CD8 + <1.2 ( OR=3.016, 95% CI: 1.695-5.366) were risk factors for severe RSV pneumonia in preschool children ( P<0.05). Conclusions:Autumn and winter, low birth weight infants, history of respiratory infections within 3 months, delayed treatment, low albumin, and low CD4 + /CD8 + are related to the occurrence of severe RSV pneumonia in preschool children. Therefore, it is necessary to strengthen the attention to the condition of preschool RSV infected children with the above risk factors, and actively intervene in controllable factors to reduce the risk of severe pneumonia.

Objective:To investigate the value of nomogram based on radiomics features of CT enterography (CTE) combined with clinical characteristics to predict secondary loss of response (SLOR) after infliximab (IFX) treatment in patients with Crohn′s disease (CD).Methods:This study was a case-control study. Clinical and imaging data of 155 patients with CD diagnosed at the First Affiliated Hospital of Anhui Medical University from March 2015 to July 2022 were retrospectively collected. The patients were divided into a training set ( n=108) and a testing set ( n=47) in the ratio of 7∶3 by stratified sampling method. All patients were treated according to the standardized protocol and were classified as SLOR (43 in the training set and 18 in the testing set) and non-SLOR (65 in the training set and 29 in the testing set) according to treatment outcome. Based on the data from the training group, independent clinical predictors of SLOR after IFX treatment were screened in the clinical data using univariate and multivariate logistic regression analysis to establish a clinical model. Intestinal phase images were selected to be outlined layer by layer along the margin of the lesion to obtain the volume of the region of interest to extract the radiomics features. The radiomics features were screened using univariate analysis and the minimum absolute shrinkage and selection operator to establish the radiomics model. Multivariate logistic regression analysis was used to build a combined clinical-radiomics model based on the screened clinical independent predictors and radiomics characters, then a nomogram was drawn. The predictive efficacy of the 3 models for SLOR after IFX treatment was assessed by receiver operating characteristic curves, and the area under the curve (AUC) was calculated. The decision curve analysis was applied to evaluate the clinical utility of the models. Results:Disease duration ( OR=1.983, 95% CI 1.966-2.000, P=0.046) and intestinal stenosis ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as the independent predictors of SLOR in the clinical data, and a clinical model was established. Totally 9 radiomics features were included in the radiomics model. The AUCs of clinical, radiomics, and combined models for predicting SLOR after IFX treatment in CD patients were 0.691 (95% CI 0.591-0.792), 0.896 (95% CI 0.836-0.955), and 0.910 (95% CI 0.855-0.965) in the training set, and 0.722 (95% CI 0.574-0.871), 0.866 (95% CI 0.764-0.968), and 0.889 (95% CI 0.796-0.982) in the testing set. Decision curve analysis in the testing set showed higher net clinical benefits for both the radiomics model and combined model than the clinical model, and combined model had higher net clinical benefits than the radiomics model over most threshold probability intervals. Conclusions:CTE-based radiomics model can effectively predict SLOR after IFX treatment in patients with CD, and a combined model by incorporating clinical characteristics of disease duration and intestinal stenosis can further improve the predictive efficacy.

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

Objective:To study the characteristics of clinical, laboratory, imaging, genetic and differential diagnosis of McLeod syndrome.Methods:The clinical characteristics of 2 cases of McLeod syndrome confirmed by gene detection in Qilu Hospital (Qingdao) on June 27, 2018 and in Qilu Hospital of Shandong University on September 11, 2019 were analyzed retrospectively. And the characteristics of patients of McLeod syndrome reported in China were analyzed in combination with literature review.Results:Both of the 2 patients were adult male, aged 57 and 61 years, respectively, with a slowly progressive course, beginning with gradually involuntary movement of trunk and extremities, involving involuntary biting of the tongue and dysphagia. Two patients had mild cognitive impairment; one patient had emotional agitation. Imaging study showed atrophy of caput nuclei caudate. Neuroelectrophysiological examination of case 1 showed sensory axon neuropathy in both upper limbs with severe damage to the left ulnar nerve. Creatine kinase (CK) was mildly elevated in 2 patients. The peripheral blood smear of 1 patient showed increased acanthocytes, accounting for 13%, the other patient showed no increased acanthocyte. McLeod syndrome related gene was tested in the 2 patients, case 1 with deletion mutation of exon 2 of XK gene, and case 2 with hemizygotic mutation of XK gene c.898delC p.L300 *. Conclusions:The clinical manifestations of McLeod syndrome are various and the differential diagnosis is crucial. For elderly male with cephalic facial chorea, elevated CK level and neuromuscular diseases, the possibility of McLeod syndrome should be screened.

ObjectiveTo explore the relationship between occupational stress， psychological capital and insomnia among nurses， and to test the mediating effect of psychological capital on the relationship between nurses' occupational stress and insomnia. MethodsStratified random sampling method was utilized in selecting 810 nurses from a tertiary A-level hospital from March to May 2021. The Effort-Reward Imbalance questionnaire （ERI）， Psychological Capital Questionnaire （PCQ） and Athens Insomnia Scale （AIS） were used to evaluate the occupational stress， psychological capital and insomnia of nurses， respectively. Then the mediation effect of psychological capital on the relationship between occupational stress and insomnia in nurses was tested by PROCESS macro program. ResultsA total of 658 （81.23%） questionnaires were effectively collected. Analysis found that nurses' effort-reward ratio was positively correlated with AIS score （r=0.379， P<0.01）， and negatively correlated with PCQ score （r=-0.275， P<0.01）. Nurses' PCQ score was negatively correlated with AIS score （r=-0.402， P<0.01）. Nurses' occupational stress could negatively predict psychological capital （β=-11.024， t=-7.324， P<0.01）， and positively predict insomnia （β=4.117， t=10.478， P<0.01）. Psychological capital could negatively predict insomnia （β=-0.087， t=-9.083， P<0.01）. The predictive effect of occupational stress on insomnia was statistically significant with psychological capital introduced as a mediating variable （β=3.158， t=8.185， P<0.01）. ConclusionPsychological capital plays a partial mediating role in the relationship between occupational stress and insomnia in nurses.

The "quality-oriented education" is closely integrated with the problem-based learning(PBL) teaching mode. In the teaching of Technologies for Microbial Detection course, the PBL teaching mode is the carrier, the student is the host, and the brainstorm guides the students to conduct "dialectical thinking", so as to cultivate the students' "innovation", "social morality" and "self-learning ability". We choose the interactive platform of "WeChat" and "MosoInk WebSite" to make up for the deficiency of PBL teaching in the large class, and comprehensively assess students' knowledge and skills, humanistic quality, and value judgment.

Objective:To evaluate the application value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and dynamic contrast enhancement MRI (DCE-MRI) in the prediction of the early efficacy of concurrent chemoradiotherapy (CCRT) for cervical squamous cell carcinoma.Methods:Fifty patients with cervical squamous cell carcinoma confirmed by pathology were included. Before CCRT, IVIM-DWI and DCE-MRI were scanned, and the values of quantitative parameters including ADC, D, D * and f of IVIM-DWI and K trans, K ep, V e and V p of DCE-MRI before treatment were measured for all patients. MRI reexamination was performed 1 month after the end of CCRT, and all patients were divided into the cure group and the residual group according to the tumor remission. The parameters of IVIM-DWI and DCE-MRI before treatment were statistically compared between two groups. The optimal predictive parameters and predictive thresholds were determined by drawing the receiver operating characteristic (ROC) curve. Results:Twenty-four patients were assigned into the cure group and twenty-six patients in the residual group. The ADC, D and V e values before treatment in the cure group were significantly lower than those in the residual group (all P<0.05), whereas the f and K trans values were significantly higher than those in the residual group (both P<0.05). The other parameters did not significantly differ between two groups (all P>0.05). The area under ROC curve (AUC=0.823) of D value was the largest, followed by K transvalue (AUC=0.754). The combined prediction efficacy of D and K trans (AUC=0.867) was higher than that of either D or K trans alone. The sensitivity was 88.5%, 85.8% and 88.8%, and the specificity was 70.8%, 66.7% and 79.2%, respectively. Conclusions:Quantitative parameters of IVIM-DWI and DCE-MRI before treatment have certain predictive value for the early efficacy of CCRT in cervical squamous cell carcinoma, among which the predictive efficacy of D value is the highest, and the combined application of D and K trans can improve the predictive efficacy.

Objective To explore the effect of application of task-based learning with experiential teaching on nursing clinical decision making ability. Methods A total of 96 nursing students were divided into experimental group and observation group with each of 48 nursing students. The experimental group used the application of task-based learning with experimental teaching, the control group used the traditional scenario simulation. At the end of the course, the final scores, skill operation scores and nursing students'evaluation of the course and clinical decision-making ability of nursing were observed in the two groups. Results The final scores, chapters related to task-based learning with experiential teaching, skill operation scores was (82.06±0.98), (12.01±0.88), (94.99±0.34) points in the experimental group, and (78.34±0.98), (9.32±0.76), (91.87±0.98) points in the control group, and the difference was significant(t=12.958, 9.872, 10.834, all P<0.01). The evaluation of teaching methods, teaching process and teaching effect was (20.06±0.98), (23.01±0.88), (35.99±0.34) points in the experimental group, and (17.34±0.98), (20.32±0.76), (30.87±0.98) points in the control group, and the difference was significant (t=5.96, 6.87, 6.99, all P<0.01).The score of clinical decision-making ability of nursing was (137.50 ± 12.61) points in the experimental group, and (123.88±9.89) points in the control group,and the difference was significant (t=5.891, P<0.01). Conclusions The effect of task-based learning with experiential teaching in teaching of nursing in vocational nursing students, enable students to transfer knowledge and experience in experience, it can improve the students' clinical decision making ability.

Objective To investigate the serum levels of dickkopf-related protein 1 (DKK1) and sclerostin (SOST) in patients with axial spondyloarthritis treated with selective cyclo-oxygenase 2 inhibitor and its relation to clinical efficacy.Methods A randomized double-blind controlled trial with axial spondyloarthritis (ax-SpA) was carried out in our hospital.The data from patients in a single center was collected and analyzed.Serum DKK1 and SOST levels were measured by enzyme-linked immuno sorbent assay (ELISA)method before and after 12 weeks treatment,then correlation analysis were conducted for DKK1 and SOST levels with erythrocyte sedimentation rate (ESR),C reactive protein (CRP),Bath ankylosing spondylitis disease activity index (BASDAI),Bath ankylosing spondylitis functional index (BASFI) and SPARCC of the sacroiliac joint inflammation score.Chi-square tests were used for analyzing of categorical data.Fisher exact tests were performed when the expected frequencies were less than 5.Two independent samples t-test was used to compare the difference between groups.Single sample t-test was used to ompare the differences between data before and after treatment.Pearson or Spearman correlation was used for correlation analysis.Results After 12 weeks of treatment,a total of 116 patients completed the follow-up,including 57 cases of imrecoxib group and 59 cases of the celecoxib group.There were no statistically significant difference between the two groups (P＞0.05).The level of serum DKK1 was significantly increased after treatment [(393±137) pg/ml,vs (542±274)pg/ml,P＜0.05].The serum level of SOST increased significantly [(39±19) pg/ml vs (57±36) pg/ml,t=5.814,P＞0.05],too.The difference between the two groups was not statistically significant (P＞0.05).Spearman correlation analysis showed that serum DKK1 was positively correlated with serum SOST (r=0.226,P=0.015).A significantcorrelation was found between SOST level and ESR,CRP,finger to floor distance,left and fight lumbar side flexion and Schober's test (ESR:r=-0.379,P＜0.01;r=-0.309,P=0.001;r=-0.225,P=0.015;r=0.185,P=0.047;r=0.247,P=0.008;r=0.214,P=0.021).Conclusion Imrecoxib and celecoxib have similar efficacy on relieving the signs and symptoms of patients with ax-SpA.Short-term application of selective COX-2 inhibitors can increase DKK1 and SOST and possibly delay radiographic progression.