BACKGROUND:Exercise improves Alzheimer's disease,dementia,and age-related cognitive abilities.A potential mediator between exercise and these health benefits may be adult hippocampal neurogenesis.Therefore,it is of great significance to explore whether and how exercise affects the adult hippocampal neurogenesis process in Alzheimer's disease mice. OBJECTIVE:To observe the effect of aerobic exercise on adult hippocampal neurogenesis of Alzheimer's disease mice,and to explore whether aerobic exercise can promote their adult hippocampal neurogenesis. METHODS:Three-month-old wild-type(C57BL/6Jnju)and APP/PS1 double transgenic Alzheimer's disease mice were randomly divided into four groups:wild control group,wild exercise group,Alzheimer's disease control group and Alzheimer's disease exercise group,with 20 mice in each group.The control group did not do exercise,and the exercise group did aerobic exercise for 5 months.After exercise intervention,real-time PCR,immunofluorescence and western blot assay were used to detect the expression levels of DCX,Ki67,βIII-tubulin and NeuN in the hippocampal tissue of mice in each group. RESULTS AND CONCLUSION:The expressions of DCX,βIII-tubulin and NeuN in the hippocampal dentate gyrus in the Alzheimer's disease control group were significantly lower than those in the wild control group(P<0.05).The expressions of DCX,Ki67,βIII-tubulin and NeuN were significantly higher in the hippocampal dentate gyrus in the Alzheimer's disease exercise group than those in the Alzheimer's disease control group(P<0.05).It is indicated that long-term aerobic exercise intervention can strengthen the proliferation,migration and differentiation of neurons during adult hippocampal neurogenesis and significantly increase the number of neuronal precursor cells and new neurons in Alzheimer's disease mice.

BACKGROUND:β-amyloid protein and Tau protein have adverse effects on the cognitive function of Alzheimer's disease patients,and Notch1 and Caspase-3 can regulate the expression of β-amyloid protein and Tau protein.It is not clear whether Notch1 and Caspase-3 mediate the process of aerobic exercise to improve the cognitive ability of Alzheimer's disease patients.At present,there is a lack of studies on the effect of long-term aerobic exercise on the expression of Notch1 and Caspase-3 in the hippocampus of Alzheimer's disease mice. OBJECTIVE:To observe the expression of Notch1 and Caspase-3 in the hippocampus of Alzheimer's disease mice undergoing long-term aerobic exercise and to investigate the effects of Notch1 and Caspase-3 in Alzheimer's disease mice. METHODS:Wild type and APP/PS1 double-transgenic Alzheimer's disease mice aged 3 months were randomly divided into four groups:wild control group,wild exercise group,Alzheimer's disease control group and Alzheimer's disease exercise group,with 20 mice in each group.Mice in the control groups were not subjected to exercise,while those in the exercise groups received aerobic exercise intervention for 5 months.After the exercise intervention,Morris water maze was used to detect the spatial learning and memory ability of mice.Real-time PCR,immunofluorescence and western blot were used to detect the expressions of Aβ1-42,Tau,Notch1 and Caspase-3 in the hippocampal tissues of mice in each group. RESULTS AND CONCLUSION:The spatial learning and memory ability of Alzheimer's mice was significantly worse than that of wild-type mice(P＜0.05).The spatial learning and memory ability of mice in the exercise groups were significantly better than that in the corresponding control groups(P＜0.05).The expressions of Aβ1-42,Tau,Notch1 and Caspase-3 in the hippocampus were significantly higher in the Alzheimer's disease control group than the wild control group(P＜0.05)and were significantly lower in the Alzheimer's disease exercise group than the Alzheimer's disease control group(P＜0.05).To conclude,long-term aerobic exercise can improve the spatial learning and memory ability of Alzheimer's disease mice,which may be related to the decreased expression of Notch1,Caspase-3,Aβ1-42 and Tau protein in the hippocampus of Alzheimer's disease mice.

BACKGROUND:Abnormal Notch1 signaling pathway is mostly found in the brain of Alzheimer's disease patients,but the role of these signaling pathways in the pathogenesis of Alzheimer's disease has not been fully clarified.Long-term aerobic exercise can alter the expression of Notch1 by affecting the methylation rate of factors related to the Notch1 signaling pathway.However,it is not clear whether aerobic exercise affects hippocampal nerve cell proliferation and histopathological features of Alzheimer's disease mice through the Notch1 signaling pathway. OBJECTIVE:To observe the effects of aerobic exercise on the proliferation and histopathological features of hippocampal nerve cells in Alzheimer's disease mice after DAPT inhibited the Notch1 signaling pathway. METHODS:APP/PS1 double transgenic Alzheimer's disease mice aged 3 months were randomly divided into four groups:control group,exercise control group,inhibitor group,and exercise inhibitor group,with 20 mice in each group.The control group was fed naturally,and the exercise group received aerobic exercise intervention.Both natural feeding and exercise intervention lasted for 20 weeks.The mice were injected with solvent or Notch1 inhibitor at week 18.After 20 weeks,the brain tissue was collected,and Aβ1-42,Tau,Ki67,and Notch1 expression levels were detected by real-time PCR,immunofluorescence,and western blot assay. RESULTS AND CONCLUSION:Compared with the control group,the expressions of Ki67 and Notch1 in the dentate gyrus region of the hippocampus were significantly decreased in the inhibitor group(P<0.05),but there were no significant differences in Aβ1-42 and Tau.The expression of Ki67 in the dentate gyrus region of the hippocampus in the exercise control group was significantly higher than that in the control group,while the expressions of Aβ1-42,Tau,and Notch1 were significantly lower than those in the control group(P<0.05).The expressions of Aβ1-42,Tau,Ki67,and Notch1 in the dentate gyrus region of the hippocampus of the exercise inhibitor group were not significantly different from those of the inhibitor group.In conclusion,the Notch1 signaling pathway may mediate exercise to improve the proliferation and histopathological features of hippocampal nerve cells in Alzheimer's disease mice.

Objective To describe the features of clinical,imaging and cerebral spinal fluid (CSF) of listerial rhombencephalitis to improve the understanding of this disease in clinical practice.Methods All the clinical data of three cases of listerial rhombencephalitis from April to August 2017 in Qilu Hospital were collected and analyzed retrospectively.Results All the three cases were healthy adult women before,with a rapidly progressive course,beginning with fever (38.2-40 ℃),headache accompanied by nausea and vomiting,followed by cranial paralysis,dysphagia and paralysis of the limbs on the 2nd to 5th day of onset,and developed to acute respiratory failure and unconsciousness on the 5th to 8th day of onset.All the three patients were diagnosed with CSF culture positive for Listera monocytogenes on the 3rd to 5th day after admission.The initial CSF lactic acid increased significantly,representing 12.3,12.0 and 10.0 mmol/L respectively;CSF white blood cells were 416× 106/L,760× 106/L and 793× 106/L,respectively,and the protein levels were 0.76 g/L,0.57 g/L and 1.47 g/L,respectively.Brain images showed brain stem was involved in all the three patients,therein cases 1 and 3 with cerebellar hemisphere involved,case 2 with upper cervical spinal cord involved,and case 1 with supratentorial hydrocephalus involved.After treatment with sensitive antibiotics,case 1 recovered,case 2 died,and case 3 lived with dysphagia.Conclusions Listerial rhombencephalitis should be suspected when a patient started with fever and headache,rapidly progressed to cranial nerve paralysis,brainstem symptoms,and acute respiratory failure,especially when the brain imaging suggested brainstem involved with increased white blood cells and apparently elevated lactic acid level of CSF.The earlier the sensitive antibiotics initiated,the better the patients' prognosis.

Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.

We wished to ascertain the prevalence as well as the genetic and antigenic variation of infectious bronchitis viruses (IBVs) circulating in the Guangxi Province of China in recent years. The S1 gene of 15 IBV field isolates during 2012-2013 underwent analyses in terms of the similarity of amino-acid sequences, creation of phylogenetic trees, recombination, and serologic identification. Similarities in amino-acid sequences among the 15 isolates of the S1 gene were 54.3%-99.6%, and 43.3%-99.3% among 15 isolates and reference strains. Compared with the vaccine strain H120, except for GX-YL130025, the other 14 isolates showed a lower similarity of amino-acid sequences of the S1 gene (65.1-81.4%). Phylogenetic analyses of the S1 gene suggested that 15 IBV isolates were classified into eight genotypes, with the predominant genotype being new-type II. Recombination analyses demonstrated that the S1 gene of the GX-NN130048 isolate originated from recombination events between vaccine strain 4/91 and a LX4-like isolate. Serotyping results suggested that seven serotypes prevailed during 2012-2013 in Guangxi Province, and that only one isolate was consistent with the vaccine strain H120 in serotype (which has been used widely in recent years). The serotype of recombinant isolate GX-NN130048 was different from those of its parent strains. These results suggested that not only the genotype, but also the serotype of IBV field isolates in Guangxi Province had distinct variations, and that increasing numbers of genotypes and serotypes are in circulation. We showed that recombination events can lead to the emergence of new serotypes. Our study provides new evidence for understanding of the molecular mechanisms of IBV variations, and the development of new vaccines against IBVs.
Animals ; Antibodies, Viral ; blood ; Chickens ; China ; Coronavirus Infections ; blood ; veterinary ; virology ; Genetic Variation ; Genotype ; Infectious bronchitis virus ; classification ; genetics ; immunology ; isolation & purification ; Molecular Sequence Data ; Phylogeny ; Poultry Diseases ; blood ; virology ; Sequence Homology, Amino Acid ; Spike Glycoprotein, Coronavirus ; chemistry ; genetics ; immunology

Objective To explore the distribution of age,reasons for treatment,risk factors,and causes of vulvovaginitis in prepubertal girls.Methods A total of 4 214 prepubertal girls with vulvovaginitis who were admitted to the Girl's Sub-department,Zhongshan Boai Hospital from January 2010 to June 2013 was reviewed retrospectively.All clinical data were from medical records with files.Results Atotalof1 587 patients (37.7％) was0to1 years old,954 (22.6％) ＞ 1 to3 years old,1 289 (30.6％) ＞ 3 to 7 years old,and 384 (9.1％) ＞ 7 years old.Many risk factors were associated with vaginitis,including poor hygiene (2 924 girls; 69.4％),allergies and exposure to allergens (875 girls; 20.8％).Most common reason for treatment was a referral from physical examination accounting for 919 girls (21.8％),followed by vaginal secretions 812 girls (19.3％).The causes of vulvovaginitis of all patients were evaluated,1 771 of which (42.0％) were nonspecific vulvovaginitis,1 309 (31.1％) labial adhesions,375 (8.9％) bacterial vulvovaginitis,266 (6.3％) allergic vulvovaginitis,and 266 (6.3％) affective leg rubbing action.Conclusions Prepubertal vulvovaginitis occurred mainly in infancy and preschool.Floating population was common.They were caused by many risk factors including poor hygiene,allergies,poor urination habits,etc.The most common causes of vulvovaginitis were nonspecific vulvovaginitis and labia adhesion,yet allergies and affective leg rubbing action were the more common causes of recurrent vulvovaginitis.We propose that focusing on girls' reproductive health,timely treating allergic and crossing rub legs and other diseases would help reduce the prevalence of vulvovaginitis in the prepubertal girls.

Objective To explore the lowest effective dosage of mifepristone combined with misoprostol in terminating ultra-early pregnancy.Methods All the cases of ultra-early pregnancy classified by amenorrhea days,β-hCG and vaginal B-ultrasonic were randomly divided into two groups.One hundred cases in G1 group (minimized dosage) were orally administered 25 mg mifepristone once a day for 2 days and combined with 200 μg misoprostol 48 hours later,while 150 mg mifepristone combined with 600 μg misoprostol 48 hours later were given to 100 cases in G2 group (normal dosage).All cases were observed for 6 hours after taking misoprostol and returned for assessment three days later.Results None missing.Expulsion of conceptus:G1 and G2 group were 22 (22.0％,22/100) and 25 (25.0％,25/100;P ＞ 0.05).Failure rate:cases with incomplete abortion were 1 (1.0％,1/100) and 2 (2.0％,2/100) in G1 and G2 group,hospitalization for suspected ectopic pregnancies both was 1 (1.0％).Bleeding:bleeding cases during the administration of mifepristone in G1 and G2 group were 71 (71.0％,71/100) and 78 (78.0％,78/100; P＞0.05); the mcan bleeding time were (5.3 ± 1.4) days and (6.0± 1.5) days (P ＜0.01).Other side effects:in G1 group,majority showed light nausea (7.0％,7/100) and light abdominal pain (20.0％,20/100).Menses recovery:99 (99.0％,99/100) for G1 group and 98 (98.0％,98/100) for G2 group to recovery on scheduled time.Satisfactions:both were 99 (99.0％,99/100).Except mean bleeding days and side-effects,the differences above showed no significance (P ＞ 0.05).Conclusion It is safe and effective treatment with the lowest dosages of mifepristone and misoprostol to terminate ultra-early pregnancies.

Objective To study the effects of X-ray radiation on CC-chemokine receptor 7(CCR7) expression in human non-small cell lung cancer (NSCLC) cells.Methods Humanadenocarcinoma cells of the line A549 were cultured and irradiated by X-ray at the absorbed doses of 2,4,6,and 8 Gy respectively by linear accelerator (with the source skin distance of 100 cm and dose rate of 442.89 cGy/min).The relative levels of CCR7 mRNA and protein expression in the A549 cells were respectively detected by real time-PCR and Western blotting 4,12,24,48,and 72 h after radiation.Untreated A549 cells were used as control group.Results The expression levels of CCR7 mRNA and protein in the A549 cells began to increase since 4 h after radiation and then decreased gradually after they reached the peak.The CCR7 mRNA expression levels 72 h after radiation of the 6 and 8 Gy groups were still significantly higher than those of the control group (t = 6.75-7.26,both P < 0.01),and the CCR7 protein expression levels of the 2 and 6 Gy group were still significantly higher than those of the control group(t=11.13-14.17,both P <0.01).Then the CCR7 protein expression levels of the 4 and 8 Gy groups decreased to the control group level 48 and 72 h after radiation respectively.Conclusions The CCR7 mRNA and protein expression levels in the NSCLC cells increase after X-ray irradiation,which may be correlated with the promotion of proliferation and metastasis of NSCLC cells by X-ray irradiation at a certain dose.

Objective To study the dose-and time-effects of X-ray irradiation on the expression of Pokemon gene in A549 cells of human lung adenocarcinoma.Methods A549 cells were cultured in vitro and exposed to X-rays with the doses of 2,4,6 and 8 Gy,respectively.Untreated A549 cells were used as control group.The relative levels of Pokemon mRNA expression in the cells were detected by using quantitative real-time PCR at 2,4,8,12,24,48 and 72 h after irradiation.Results The Pokemon mRNA expression levels decreased in the early period after irradiation(except 2 and 4 h after irradiation in 2 Gy group)and then increased in the later stage(48 h after irradiation)with significant statistical differences at the most time points in comparison with the control group(t=3.40-154.76,P<0.05).Conclusions Higher doses of X-rays may degrade the expression of Pokemon mRNA in the human A549 cells and induce apoptosis in the early period,hut also may upgrade its expression in the later period, which might be correlated with the cell cycle regulation and DNA damage repair in the A549 cells.