Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.

Objective To study the role and mechanisms of equilibrative nucleotide transporter 1(ENT1)on Alzheimer's disease(AD)by constructing ENT1 overexpression and knockdown plasmids.Methods Molecular cloning was used to construct the ENT1 overexpression(pAAV-ENT1-mCherry)and knockdown(pAAV-ENT1shRNA-ZsGreen)plasmids.The overexpression plasmids and the knockdown plasmids were transfected into N2A cells(mouse Neuro A2 cells)and N2A-APP cells(N2A cells stably expressing human APP695).The expression of ENT1 and inflammatory factors at mRNA and protein levels were detected by real-time qPCR and Western blotting,respectively,and the change in cell viability were measured with CCK-8 assay.Results Sequencing and real-time qPCR indicated that ENT1 overexpression and knockdown plasmids were successfully constructed.CCK-8 assay showed that ENT1 overexpression significantly reduced the cell survival rate within 24 h(P＜0.05),while its knockdown increased the cell survival rate(P＜0.01).Real-time qPCR displayed that overexpression of ENT1 enhanced the expression levels of inflammatory factors,such as IL-1β,TNF-α,C1q-a and C1q-b in N2A cells(P＜0.05),while ENT1 knockdown reversed the above changes in inflammatory factors in N2A-APP cells(P＜0.05).Conclusion Knockdown of ENT1 attenuates pathological changes in AD by reducing the inflammatory response.ENT1 may be a potential target in the pathological mechanism of AD.

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus

Objective:To explore the reproductive health status of the female street cleaners in Chaoyang district of Beijing and its influencing factors.Methods:In July 2018, a total of 647 questionnaires were sent out to female road cleaning and sanitation workers in the whole district, 613 of which were valid, with an effective rate of 94.7%. Frequency or percentage (%) is used for statistical description of counting data, and mean standard deviation is used for measurement data. The influencing factors were analyzed by 2 test.Results:The average age of 613 female road sweepers in Chaoyang District of Beijing was 42.01 (SD=6.69) years old, including 535 married female workers (87.28%) , 356 middle school and below educated (58.08%) , 292 non Beijing registered (47.63%) , accounting for (/613) , (/613) female workers working hours >8 hours per day 110 (17.94%) , weekly rest <2 days 341 (55.63%) . 144 (23.49%) women workers did not have regular gynecological examination, 119 (19.41%) had reproductive tract infections, 177 (28.87%) had abnormal menstruation in recent 6 months. Drinking, sexual behavior outside marriage, night shift and job satisfaction were all the influencing factors ( P<0.05) . The increasing age, working years, drinking, household registration in other places and the decreasing satisfaction of women workers＇ rights and interests protection were all the influencing factors ( P<0.05) . Conclusion:The reproductive health status of female road sweepers in Chaoyang District of Beijing is not optimistic.

Objective:To explore the reproductive health status of the female street cleaners in Chaoyang district of Beijing and its influencing factors.Methods:In July 2018, a total of 647 questionnaires were sent out to female road cleaning and sanitation workers in the whole district, 613 of which were valid, with an effective rate of 94.7%. Frequency or percentage (%) is used for statistical description of counting data, and mean standard deviation is used for measurement data. The influencing factors were analyzed by 2 test.Results:The average age of 613 female road sweepers in Chaoyang District of Beijing was 42.01 (SD=6.69) years old, including 535 married female workers (87.28%) , 356 middle school and below educated (58.08%) , 292 non Beijing registered (47.63%) , accounting for (/613) , (/613) female workers working hours >8 hours per day 110 (17.94%) , weekly rest <2 days 341 (55.63%) . 144 (23.49%) women workers did not have regular gynecological examination, 119 (19.41%) had reproductive tract infections, 177 (28.87%) had abnormal menstruation in recent 6 months. Drinking, sexual behavior outside marriage, night shift and job satisfaction were all the influencing factors ( P<0.05) . The increasing age, working years, drinking, household registration in other places and the decreasing satisfaction of women workers＇ rights and interests protection were all the influencing factors ( P<0.05) . Conclusion:The reproductive health status of female road sweepers in Chaoyang District of Beijing is not optimistic.

Objective: To establish an accurate and selective UPLC-MS/MS) method for the determination of afatinib in rat plas-ma. Methods: Protein precipitating by acetonitrile was used to prepare the samples. A CORTECS BEH C18column ( 50 mm × 2. 1 mm, 1. 6 μm) was used to separate the analytes at 40℃. The mobile phase consisted of acetonitrile and water (0. 1% formic acid) with the flow rate of 0. 4 ml·min-1. The analytes were quantified by multiple reaction monitoring ( MRM) mode with positive electrospray ionization, while the target fragment ions were m/z 486. 19→112. 1 for afatinib and m/z 557. 3→112. 15 for neratinib (IS). Results: The calibration curve obtained good linearity for afatinib within the range of 1–200 ng·ml-1(r=0. 998 1), and the LLOQ in rat plasma was 1. 0 ng/ml. The intra-and inter-day precisions were both≤9. 51% . The recovery of afatinib from plasma was above 77. 1% . After intragastric administration and intravenous administration of afatinib in rats, the t1/2was 7. 19 h and 2. 69 h, Cmax was 97. 78 ng·ml-1and 123. 37 ng·ml-1,and AUC(0-∞)was 1 505. 4 ng·ml-1·h and 405. 55 ng·ml-1·h, respectively. Con-clusion: The validated method can be applied in the pharmacokinetic study of afatinib at the intragastric and intravenous dosage of 10 and 2 mg·kg-1, respectively.

Objective To investigate the mechanism and effect of the spinal cord outlet of the skull base on Chiari Ⅰ malformation with syringomyelia.Methods The cervical spinal cord stem angle (Anbc),slope angle of cervical vertebra (Ansc) of Chiari Ⅰ malformation were measured.In foramen magnum (Llf) and anterior vertebral canal level (Laf),spinal canal(Ac),spinal cord (As) and inferior hernia area (Ah) were measured.Angle,area and ratio were compared in Chiari Ⅰ malformation with syringomyelia,Chiari Ⅰ malformation without syringomyelia and normal control group.Results Ansc,Anbc-Ansc had significant differences among control group and Chiari Ⅰ malformation patients (all P＜0.001).In Llf,Laf,As had significant differences among three groups (all P＜0.05),further comparison of the two showed there were significant differences between Chiari Ⅰ malformation with syringomyelia patients and control group,Chiari Ⅰ malformation without syringomyelia patients and control group in Llf(all P＜0.05).In Llf,Laf,Ac in Chiari Ⅰ malformation with syringomyelia was smaller than control group (P＜0.05).Ah in Llf,Lafand Lh in Llf had no statistical significant difference between Chiari Ⅰ malformation with and without syringomyelia patients (all P＞0.05).In Llf,Laf,As/Ac had statistical significant difference among Chiari Ⅰ malformation with and without syringomyelia patients,control group (all P＜0.001),further comparison of the two showed As/Ac in Llf had statistical significance difference between Chiari Ⅰ malformation with syringomyelia patients and control group (P＜0.05),As/Ac in La had statistical significance difference between Chiari Ⅰ malformation with syringomyelia patients and control group,between Chiari Ⅰ malformation without syringomyelia patients and control group (all P＜0.05),Conclusion The cervical spinal cord,Ansc reducing,narrow vertebral proportion increase are important factors to promote Chiari Ⅰ malformation syringomyelia.

According to the points and difficulties of aminophylline monitoring experiments, oriented by problems, specific teaching case was designed to practice case teaching. The analysis of the results of classroom performance, teaching effect evaluation, peer evaluation and students' feedback showed that case teaching promoted the initiatives of students' learning as well as improved the teaching effect compared with the traditional teaching method. Furthermore, it improved their clinical thinking ability through theory and practical cases and helped the teachers to learn while teaching.

Objective The aim of this study is to understand the impairment and compensation mechanism of brain function in untreated primary insomnia (PI) patients.The approach of fractional amplitude of low frequency fluctuation (fALFF) is used to analyze raw data between the PI patients and the normal control group in resting state using functional magnetic resonance imaging (fMRI).Methods Fifty-nine PI patients,admitted to our hospital from November 2015 to November 2016,and 47 age-,education-,and gender-matched normal healthy subjects were chosen in our study.Pittsburg sleep quality index (PSQI),insomnia severity index (ISI) were employed to evaluate the sleep quality.Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were employed to evaluate the emotion.Resting state fMRI and fALFF analyses were used to compare the functional regional activities.The correlations of fALFF data with PSQI,SAS and SDS scores were analyzed.Results In PI patients,2 had mild to moderate insomnia,41 had moderate insomnia,and 16 had serious insomnia.ISI scores in the normal healthy subjects were less than 7.The PSQI,SAS,SDS and ISI scores in the PI patients were significantly higher than those in the normal healthy subjects (P＜0.05).As compared with the control group,the PI group had significantly increased fALFF value in the right hippocampus (HIP),right parahippocampa gyms,right amygdala,and bilateral thalamus.The fALFF value was positively correlated PSQI,SASandSDSscores (r=0.582,P=0.000;r=0.617,P=0.000;r=0.653,P=0.000).Conclusion Some brain regions in the PI patients are abnormal in the resting state,which can reflex functional regional activities of PI patients.

OBJECTIVE:To determine the equilibrium solubility of albendazole(ABZ)and its apparent oil-water partition coef-ficient. METHODS:The equilibrium solubility of ABZ in various solutions was determined at 37 ℃ by HPLC and saturation solu-bility method,including water,7 kinds of common organic solvents with different polarities(methanol,ethanol,etc.),organic ac-id(oleic acid,glacial acetic acid,lactic acid,formic acid),hydrochloric acid of pH 1.2,phosphate buffer solution(PBS)of dif-ferent pHs(2.0-7.8)and 6 kinds of common surfactants with mass concentrations of 10,50 and 100 mg/ml(polysorbate 80,polox-amer,etc.). The apparent oil-water partition coefficient(P)was calculated with the concentration ratio of ABZ in oil phase(N-oc-tyl alcohol)and water phase(water and PBS of different pHs)after partition equilibrium. RESULTS:The equilibrium solubility of ABZ reached(0.26±0.02)μg/ml in water,with the lgP of 3.66±0.01. The equilibrium solubility of ABZ in common organic sol-vents and organic acids was higher than in water. The higher the polarity of the organic solvent was and the weaker of organic acid was,the weaker of its ability to solubilize ABZ would be. The equilibrium solubility of ABZ was higher in the medium of pH 1.2-2.5 than in that of pH 5.0-7.8. The ability of the surfactant to solubilize ABZ was related to its type,and the higher of the mass concentration of the surfactant was,the stronger of its ability to solubilize ABZ became. lgP was less than 1.6 at pH 1.2-2.0 and changed little at pH 5.0-7.8 [(3.71 ± 0.26)-(3.68 ± 0.26)]. CONCLUSIONS:ABZ is insoluble in water. Its equilibrium solubility demonstrates a negative correlation with the polarity of the organic solvent and a positive correlation with the acidity of the organic acid and with the mass concentration of the surfactant. It has higher water solubility and lower lipid solubility in a strong acidic en-vironment,and higher lipid solubility and weaker water solubility in weak acidic,weak basic and neutral environments.