Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

Objective To investigate the relationship between the central foveal thickness(CFT),ellipsoid zone(EZ)interruption ratio and best corrected visual acuity(BCVA)in patients with idiopathic epiretinal membranes(iERM).Methods A retrospective case-control study was conducted.The cluster sampling method was used to select 336 iERM patients(500 eyes)who underwent physical examinations in 9 community hospitals of the Kailuan Group from 2014 to 2018.Among them,215 were male(64.0％)and 121 were female(36.0％),with an average age of 31-89(66.4±8.8)years.According to the gass classification,these patients were divided into three groups:gass 0 group(201 patients,305 eyes),gass 1 group(75 patients,101 eyes),and gass 2 group(60 patients,94 eyes).Pearson correlation analysis was used to evaluate the correlation between BCVA(converted to logMAR visual acuity)and gass classification,EZ interruption ratio,CFT.Results The average BCVA(logMAR)and CFT of 500 eyes were 0.45±0.28 and(337.6±101.8)μm,re-spectively,with EZ interruption in 86 eyes(17.2％).There were statistically significant differences in BCVA(logMAR)(0.62±0.29,0.48±0.23,0.26±0.32),CFT[(283.20±79.30)μm,(335.50±84.50)μm,(394.00±135.60)μm],and EZ interruption ratio(2.6％,20.8％,60.6％)among gass 0,gass 1 and gass 2 groups(all P＜0.05).Pearson correlation analysis showed that there was no correlation between age and BCVA among different groups(r2=0.021,P=0.314);BCVA was positively correlated with CFT(r2=0.531,P=0.000),EZ interruption ratio(r2=0.304,P=0.000),and gass classification(r2=0.587,P=0.000).Conclusion The EZ interruption may occur in the early stage of iERM.BCVA is correlated with CFT,EZ interruption ratio and gass classification;the incidence of EZ interruption in gass 2 iERM signifi-cantly increases.

Objective To explore the effects of aripiprazole on clinical symptoms and neurotrophic factor levels in patients with schizophrenia. Methods Forty patients with schizophrenia and 40 normal controls were included in the study. The clinical symptoms of patients receiving aripiprazole only for 12 weeks were evaluated by using the Positive and Negative Syndrome Scale (PANSS). Stroop Color-Word Test (SCWT), Continuous Performance Test, Digit-Symbol Coding Test and Trail Making Test-A were used to evaluate the cognitive function both in patients and controls. Serum levels of Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT-3) were measured using enzyme linked immunosorbent assay. Results The clinical scores, cognitive function and levels of neurotrophic factors were different before and after treatment (P<0.01). And those were significantly lower in patients than in control group (P<0.05). Before treatment, BDNF was negatively correlated with PANSS negative symptom score (r=-0.362, P=0.022);NGF was related to the total score of PANSS (r=0.332, P=0.037) and positive symptoms (r=0.401, P=0.010); NT-3 was associated with negative symptom scores (r=-0.376, P=0.017) and SCWT-color words (r=0.332, P=0.037) in patient group. After treatment, the increase in BDNF was correlated with the reduction in PANSS total score (r=0.371, P=0.018), negative symptom score (r=0.345, P=0.029) and general pathology score (r=0.342, P=0.031). There was a correlation of the increase of NGF with the decrease of PANSS total scores (r=0.437, P=0.005) and with positive symptom scores (r=0.357, P=0.024). Conclusion Treatment with Aripiprazole can improve the clinical symptoms and cognitive functiona impairments in patients with schizophrenia, which may be related to the increase in serum levels of BDNF, NGF and NT-3.

Objective To investigate the effects of specific TrkB receptor agonist 7,8-dihydroxyflavone ( 7,8-DHF) on spatial cognitive function and synaptic structure in schizophrenia rat model. Methods SD infant rats were divided into normal control group and model group according to the random number table method on the 6th day after birth. During the postnatal day 7 to 11, rats in the normal control group received subcutaneous injection of 0.9% sodium chloride solution (1 mL·kg-1) twice daily, and the rats in the model group were injected with dizocilpine (0.1 mg·kg-1). Beginning on the postnatal day 60, model rats were randomly divided into 7,8-DHF group and model control group, which were given intraperitoneal injection of 7,8-DHF ( 5 mg·kg-1 ) and DMSO once daily for 14 consecutive days, respectively. The rats of normal control group were given equal volume injections of DMSO. Morris water maze task, Golgi staining and Western blotting were adopted to examine spatial cognitive function, hippocampal dendritic spine density, protein expression and activity, respectively. Results The result in the open field test showed that the total travelled distance within 5 min was (12.20±1.62) m in the normal control group, (11.73±1.36) m in the model control group and (12.94±1.09) m in the 7,8-DHF group. The escape latency and travelled distance in the model control group were significantly higher than those in the normal control group (P<0.05), and the escape latency and travelled distance in rats of 7,8-DHF group were significantly shortened as compared with those in the model control group (P<0.05). There was no significant difference in the swimming speed among the three groups (P>0.05). The hippocampal dendritic spine density was (14.2±2.3)/10 μm in the normal control group, (8.0±1.9)/10 μm in the model control group, and (13.5±1.7)/10 μm in the 7,8-DHF group, the differences between the three groups were significant ( all P<0.05);the phosphorylation level of GluR1 protein was (100.0±5.0) in the normal control group, (47.9±10.8) in the model control group, and (97.5±9.3) in the 7,8-DHF group, and the differences among the three groups were significant ( all P<0. 05 ) . Conclusion 7, 8-DHF treatment could improve the spatial cognitive function in rat model of schizophrenia and the mechanisms might be related with the increases of hippocampal dendritic spine density and phosphorylated levels of GluR1.

Objective To explore the change of serum insulin-like growth factor-2 (IGF-2) and its relationship with clinical characteristics in patients with schizophrenia. Methods Fifty-one schizophrenic patients were recruited in the present study and 50 healthy volunteers served as controls. The serum IGF-2 level was measured using enzyme linked immunosorbent assay (ELISA). Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychotic symp?toms of patients. Trail Making Test-A (TMTA), Digit-Symbol Coding Test (DSCT), Continuous Performance Test (CPT) and Stroop Color-Word Test (SCWT) were used to evaluate the cognitive function of both groups. Results There were sig?nificant differences in the results of TMTA, DSCT, CPT and SCWT between patient and control groups. The serum levels of IGF-2 were significantly lower in patients than that in controls [(202.7±40.7) ng/mL vs. (365.9±65.5) ng/mL, P<0.01]. The levels of serum IGF-2 were not significantly different between first-episode and recurrent schizophrenic patients (P>0.05). Furthermore, significant correlations were found between the serum IGF-2 level and the negative symptom sub?scale of PANSS (r=-0.397, P=0.004), CPT score (r=0.378, P=0.006), SCWT-word number (r=0.289, P=0.040), SC? WT-color number (r=0.327, P=0.019) and SCWT-word/color number (r=0.386, P=0.005) in schizophrenic patients. Con?clusion The serum IGF-2 levels of patients with schizophrenia are significantly lower than that of healthy controls, and the IGF-2 level is associated with the severity of negative symptoms and cognitive impairments in patients, indicating that serum IGF-2 might be an indicator of the severity of schizophrenia.