Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.
Mice ; Animals ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Neurons/metabolism* ; Receptors, AMPA/metabolism* ; Disease Models, Animal

Objective:To survey the knowledge, attitudes, and practice about chronic obstructive pulmonary disease (COPD) among general practitioners in Sichuan province.Methods:From October to November 2020, a questionnaire survey on knowledge, attitudes and practice (KAP) among 104 general practitioners who participated in the training of the comprehensive prevention and control of COPD organized by Sichuan Provincial Health Commission. The content of the questionnaire included the basic information and the KAP status of COPD. The descriptive analysis, Mann-Whitney U test, and Kruskal-Wallis H were used for statistical analysis. Results:A total of 104 questionnaires were distributed and 102 were returned with a response rate of 98.1%. General practitioners with different ages, professional titles, visits of COPD patients each month, and whether or not to refer COPD patients to higher-level hospitals were not significantly different in the scores of knowledge( U=1 276.00, H=0.78, U=1 074.00, U=589.00), attitude( U=1 141.50, H=1.75, U=1 090.00, U=585.00), and practice( U=1 221.00, H=0.31, U=1 163.00, U=499.50) (all P>0.05). In knowledge part the highest correctness rate was "quitting smoking is the most powerful interventions affecting the natural disease course of COPD" (100.0%, 102/102); the lowest was that"the main objective examination for judging the airflow limitation of COPD patients is the lung function test"(5.9%, 6/102). In the part of the attitude, the highest positive rate was "educating patients to quit smoking and avoid exposure to second-hand smoke" (65.7%,67/102); the lowest positive rate was "provide exercise guidance to patients "(43.1%, 44/102) and " be responsible for long-term treatment follow-up" (43.1%, 44/102). In the part of practice, the highest behavioral rate was "when receiving patients with COPD, actively pay attention to the treatment of comorbid diseases" (95.1%, 97/102); the lowest behavioral rate was "when patients with COPD were seen at the clinic, and the patients were advised of the best time to use the inhaler" (65.7%, 67/102). Conclusions:The study indicates that the relevant departments need to increase the intensity of knowledge training for general practitioners in Sichuan province. General practitioners should continuously improve their education, prevention, and treatment ability and implement the primary responsibilities for COPD management.

Objective:To investigate the normal range of exhaled nitric oxide (FeNO) in 6-18-year-old children in China, so as to provide a data base for the establishment of FeNO standards for Chinese children.Methods:A multi-center study was conducted on 5 949 children aged 6-18 (3 101 males and 2 848 females) in 16 pro-vinces of 7 administrative districts in China.According to the technical standard recommended by American Thoracic Society/European Respiratory Association, FeNO was measured, and the relationship of FeNO with the sex, age, height, weight, body mass index and region was discussed.Results:The geometric mean FeNO value of Chinese children aged 6-18 was 14.1 ppb, and its 95% confidence interval (skewness distribution) was 1.0-38.2 ppb.The geometric mean FeNO values of children aged 6-11 and 12-18 were 13.1 ppb and 15.7 ppb, respectively, and their 95% confidence intervals (skewness distribution) were 1.0-38.1 ppb and 2.0-38.2 ppb.For children at and under 11 years old, FeNO decreased with age, with a mean decline of 1 ppb per year.The multiple linear regression results suggested that there was a significant correlation between FeNO and age for children aged 6-11, and FeNO of children aged 12-18 was significantly correlated with the gender, height, and region(all P<0.01). Conclusions:FeNO values of Chinese children and adolescents in this study are higher than those obtained by the previous study conducted from 2010 to 2012.For children aged 12-18, 16 ppb is recommended as the clinical cut-off point.For children at or under 11 years old, the influence of age on FeNO should be considered, and the cut-off point of FeNO decreases by 1 ppb as the age is reduced by one year.

Objective: To investigate the diagnostic value of non-specific diagnostic indicators for bacterial neonatal late-onset sepsis. Methods: A total of 55 children with bacterial neonatal late-onset sepsis in Langfang People's Hospital were selected as sepsis group.Another 67 cases of non-infected newborns were selected as control group.White blood cell, platelet and C-reactive protein were retrospectively analyzed for diagnostic value.Meanwhile, percentage of neutrophils and mean platelet volume were analyzed for diagnostic value. Results: When the bacterial neonatal late-onset sepsis occurred, the sensitivity(41.8%), specificity(95.6%) and positive predictive value(92.0%) of C-reactive protein were high.The sensitivity(18.2%, 10.9%), positive predictive value(71.4%, 85.7%) of white blood cell and platelet were low, but specificity(94%, 98.5%) was high.The percentage of neutrophils [(62.01±22.16)] and mean platelet volume[(11.60±0.98)] were higher than those of the control group [(36.58±11.06), (10.88±0.95)], and the differences were statistically significant(all P<0.05). Conclusion C-reactive protein has greater diagnostic value for bacterial neonatal late-onset sepsis.The percentage of neutrophils and mean platelet volume have some diagnostic value.

Objective: To explore the therapeutic effects of edaravone, oxiracetam combined with Shuxuetong on cerebral hematoma and improvement of neurological function in patients with cerebral hemorrhage. Methods: A total of 96 patients with cerebral hemorrhage were randomly divided into observation group and control group by the random number table method, with 48 cases in each group.The observation group received intravenous drip of edaravone (4.0g added into 0.9% sodium chloride injection to 250mL, intravenous drip, 1 time/d), oxiracetam(30mg added into 0.9% sodium chloride injection to 100mL solution, 30min intravenous drip, 2 times/d), and Shuxuetong injection(4mL added into 0.9% sodium chloride injection to 250mL, intravenous drip, 1 time/d) on the basis of routine treatment, and the control group was treated with routine treatment for cerebral hemorrhage.The efficacy and safety in the two groups after treatment of 21 days were observed. Results: After treatment, the neurological deficit score and cerebral hematoma volume of the two groups were improved(all P<0.05), but the improvements of the observation group was significantly better than those of the control group[(4.44±3.20)points vs.(10.53±2.86)points, (21.83±3.85)points vs.(26.71±3.49)points, (7.83±5.31)mL vs.(13.74±6.16)mL, t=9.818, 6.506, 5.035, all P<0.01]. The total effective rate of the observation group was higher than that of the control group(87.5% vs.52.1%, χ²=14.740, P<0.05). No drug-related adverse reactions occurred in two groups. Conclusion The application of oxiracetam and edaravone combined with Shuxuetong injection in patients with cerebral hemorrhage can effectively improve the brain edema and nerve defect, it has a positive significance to promote the patients' recovery after cerebral hemorrhage, and it is worthy of clinical application.

Objective To explore the effect of Shenshuaining capsule on nutritional status and blood rheology in patients with chronic renal failure.Methods 150 cases of chronic renal failure were randomly selected and were randomly divided into observation group and control group, 75 cases in each group.The control group were given hemodialysis for treatment,and the observation group was treated with Shenshuaining capsule one week after dialysis.The clinical effect,nutritional status and biochemical indicators in the two groups were observed.Results The total effective rate in the observation group was 86.67%, which was higher than 72.00% in the control group,the difference was statistically significant(x2=4.920,P<0.05).After treatment,the nutrition indicators of HBG,ALB,IgG,IgA and IgM in the observation group were (135.7±16.4)g/L,(34.5±2.9)g/L,(10.8±0.7)g/L,(2.1±0.4)g/L and (1.7±0.3)g/L respectively, which were higher than those in the control group[(113.8±16.9)g/L,(28.4±2.5)g/L,(7.6±0.8)g/L,(1.3±0.3)g/L and (1.2±0.2)g/L], the differences were statistically significant(t=8.054,13.797,26.070,13.856,12.010,all P<0.01).In the observation group,the incidence rate of undernutrition was 25.33%, which was lower than 46.67% in the control group, the difference was statistically significant(x2=45.905,P<0.05).After treatment,the blood urea nitrogen and blood urea in the observation group were (349±64)μmol/L and (10.4±3.7)mmol/L respectively,which were lower than those in the control group[(462±51)mol/L and (14.2±4.5)mmol/L], the differences were statistically significant(t=11.958,5.649,all P<0.05).After treatment,the creatinine clearance rate and concentration of hemoglobin in the observation group were (25.1±6.1)mL/min and (92.1±21.1)g/L respectively, which were higher than those in the control group[(21.7±5.4)mL/min and (84.7±15.3)g/L], the differences were statistically significant(t=3.614,2.459,all P<0.01).After treatment, the high blood viscosity,low blood viscosity,plasma viscosity and hematocrit in the observation group were (3.59±0.94)m/Pas,(7.84±0.97)mPa/s,(1.31±0.15)mPa/s and (0.33±0.07) respectively, which were lower than those in the control group[(4.41±1.13)mPa/s,(8.72±1.05)mPa/s,(1.43±0.24)mPa/s and (0.42±0.05)], the differences were statistically significant(t=11.958,5.649,2.459,all P<0.01).Conclusion For patients with chronic renal failure,Shenshuaining capsule combined with hemodialysis can improve the nutritional status and blood rheology.

Objective To detect and analyze nuclear factor kappa B (NF-κB),Helicobacter pylori (HP),Helicobacter pylori cytotoxin associated protein A (CagA),platelet (PLT) and platelet associated IgG (PA IgG) in 224 patients with idiopathic thrombocytopenic purpur(ITP) from three urban hospitals of Shaoxing,in order to explore the role of NF-κB and CagA in the pathogenesis of ITP,then to improve the prognosis of ITP.Methods SABC method was used to detect the NF-κB,13C breath test for the determination of the Hp infection.CagA and PA-IgG were tested by enzyme linked immunosorbent assay.Automatic blood cell analyzer was used to measure PLT.According to the test results,the patients were divided into Hp+cagA+NF-κB+,Hp+cagA+NF-κB-,Hp+cagA-NF-κB+,Hp+cagA-NF-κB-,Hp-NF-κB+,Hp-NF-κB-PLT groups,and PA-IgG,PLT of the six groups were statistically analyzed.Results Of 224 cases with ITP,175 cases of HP positive,the positive rate was 78.13%.CagA+ 91 cases in 175 cases of Hp+,accounting for 52%,overall 43.63%.NF-kappa B+ 108 cases,the positive rate was 46.21%,78 cases were found in Hp+cagA+,accounting for 85.71% in cagA+.In 84 cases of Hp+cagA-,there were 21 cases NF-κB+,the positive rate was 25%.In 49 of HP-,9 cases with NF-kappa B+,accounting for 18.37%.PLT and PA-IgG were compared among the groups.The count of PLT of group Hp+,group Hp+cagA+ and group NF-κB+ was lower than group Hp-,group Hp+cagA- and group NF-κB-.However,the level of PA-IgG of group Hp+,group Hp+cagA+ and group NF-κB+ was higher than group Hp-,group Hp+cagA- and group NF-κB-,the difference was statistically significant(P<0.05).Conclusion CagA maybe directly or through the activation of NF-kappa B take part in the immune response of ITP,cause PA-IgG increased and thrombocytopenia.

Objective To explore the ziggy joint amomum six columns nai jun pill in patients with diabetic nephropathy urinary inhibition c and serum c-reactive protein levels.MethodsSelect 80 patients with diagnosis of diabetic nephropathy, randomly divided into 2 groups, 40 cases in each group.Craig column nai treatment, control group given on the basis of the observation group in the control group given six jun pill treatment, treatment of 12 weeks, before and after treatment were detected blood glucose (FBG), glycosylated hemoglobin (HbA1C), urinary inhibition c (CysC) and serum c-reactive protein (CRP) and 24 h urinary microalbumin urine trace albumin (24 hUAE) changes.ResultsCompared with before treatment, 24 hUAECysC, CRP and 2 group were lower (P< 0.05);Compared with control group, 24 huae CysC, CRP and the observation group were lower (P< 0.05), the clinical curative effect is higher (P< 0.05), and high safety.ConclusionZiggy joint amomum six columns nai jun pill treatment of the diabetic nephropathy is a effective way, and can significantly reduce serum CysC, CRP levels.

Objective To study the effects of endolymphatic sac decompression and on semicircular canal plugging in treating intractable Meniere's disease.Methods A total of 14 cases of intractable Meniere's disease were included in this study.The age was from 33~67 years old and the history was from 1 to 40 years.The hearing level of bone was from 35 to 65 dB for the speech frequencies.All cases received the treatments according to the pre-op-erative design.The endolymphatic sac was decompressed and the three semicircular canal bones were drilled to cre-ate a fenestra followed by soft tissue plugging into the canal.The vertigo,hearing level and tinnitus were included in the following up.Results All cases had no facial palsy,no cerebrospinal leak,and no vertical after surgery.In the period of 3 to 18 months following up,the attack of Meniere's disease was completely controlled for 13 cases excep-tion of one lost case.For five cases,the hearing level descended 10 to 15 dB compared to pre-operation.Conclusion Although the endolymphatic sac decompression can relieve endolymphatic pressure,this may not adequately pro-tect the hearing caused by the semicircular canal plugging.The surgical technique is reliable and safe;however fur-ther clinical data should be gathered.

Objective To develop a duplex fluorescence RT-PCR assay for detection of scavenger receptor class B, typeⅠ(SRBⅠ) knockout mice. Methods Primers and probes were designed according to knockout region of SRBⅠgene and related substituted sequence. DNA samples were extracted from tails of mice and performed amplification using real-time PCR. SRBⅠgenotypes of mice were analyzed according to amplification curves of FAM and CY5 channels. Finally, the sensitivity of the method was detected and the accuracy was verified by the direct sequencing. Results The homozygous SRBⅠwild genotype showed an amplification curve only in FAM channel. When the homozygous SRBⅠknockout genotype was present, the typical S amplification curve appeared only in the CY5 channel. Heterozygous genotype showed two typical S amplification curves in both FAM and CY5 channels, respectively. The results showed that the sensitivity reached 4×101 copies/μL, and there was complete concordance between this method and direct DNA sequencing. Conclusion The new method is simple, rapid and accurate, which is suitable for genotyping SRBⅠknockout mice.