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 investigate the clinicopathological features and imaging differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) in the central nervous system (CNS).Methods:A case of CNS IVLBCL with multiple intracerebral microbleeds (CMBs) diagnosed in the Department of Neurology, Qilu Hospital of Shandong University in 2017 was reported. The clinical and imaging data, histological and immunohistochemical markers were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 31-year-old woman presented with headache and seizures. Cranial magnetic resonance imaging (MRI) showed multifocal lesions involving mainly the cortical and subcortical white matter (bilateral cerebral hemisphere and right cerebellar hemisphere), hyperintense signal on T 2-weighted and fluid-attenuated inversion recovery images, with hypointense signal on T 1-weigthed and diffusion-weighted images and contrast enhancement in some lesions. The susceptibility weighted imaging revealed multifocal cortical or subcortical hypointense lesions, involving mainly the subcortical white matter. Brain magnetic resonance angiography was normal. Brain magnetic resonance venography showed left side transverse sinus was hypoplastic. Cranial magnetic resonance spectroscopy showed decreased N-acetylaspartylglutamate peak, elevated choline peak and inverted lipid double peak. Her symptoms and the lesions once improved after starting steroid treatment. However, CNS recurrence occurred after 1 week of steroid withdrawal. She underwent the biopsy of the right frontotemporal lobe. The pathological examination showed multiple microscopic hemorrhages and edema scattered in the brain tissue. A large number of heterologous mononuclear cells were aggregated in small blood vessels in the parenchyma and meninges. Immunohistochemical analysis revealed that the tumor was negative for Epstein-Barr virus encoded small RNAs, CD 3, CD 10, cytokeratin and CD 138, and positive for CD 20, CD 79α, B-cell lymphoma (BCL)-2, BCL-6, myelocytomatosis oncogene (C-myc) and multiple myeloma oncogene-1 (MUM-1). The Ki67 proliferation index was about 70%. The diagnosis of IVLBCL was confirmed. Conclusions:IVLBCL in CNS is a rare and swiftly progressive disease with poor prognosis. Its clinical symptoms and imaging are nonspecific. Early diagnosis and treatment is critical. Biopsy is the gold standard for diagnosis. Random skin biopsy may be helpful for the early diagnosis. Furthermore, regarding the cause of multiple CMBs, the possibility of IVLBCL should be considered in the differential diagnosis, in addition to the common causes, such as primary angiitis of the CNS and cerebral amyloid angiopathy.

The successful retrieval of ancient mitochondrial DNA (mtDNA) from Neanderthals provides powerful experimental evidence that clarifies the arguments between the out-of-Africa and multiregional models of evolution. However, the lack of nuclear DNA from Neanderthal fossils and mtDNA of early modern human fossils dating back to approximately the same time in the Pleistocene constitutes a limitation that may compromise the significance of mtDNA phylogenetic analysis. In this report, we introduce a mitochromic analysis using Neanderthal mtDNA as a foreign transgene and humans as a naturally occurring transgenic species. Forty Neanderthal mtDNA retrievable nuclear fragments were identified by blasting human genome data with Neanderthal mtDNA. Five of the 40 fragments exhibited higher correlation with Neanderthal mtDNA than those with modern human mtDNA. Furthermore, these five nuclear fragments harbor Neanderthal mtDNA-unique haplotypes. Based on the 98%+ identity between Neanderthal and modern human mtDNA when compared by groups, we suggest that some of the modern human nuclear fragments retrieved using Neanderthal mtDNA may aid in decoding Neanderthal genetic information, and also may simultaneously demonstrate a close genetic evolutionary relationship between modern humans and Neanderthals.

Objective:To explore the application effect of online and offline mixed teaching based on DingTalk platform in clinical practice teaching of respiratory department.Methods:The Batch 2016 ( n= 40) and Batch 2017 ( n=47) undergraduates of clinical medicine in Qiqihar Medical College were selected as the research objects, and they were divided into a control group and a research group. The control group adopted traditional offline theoretical teaching, while the research group adopted online-offline mixed teaching, focusing on teaching design and teaching objectives, teaching subjects, teaching resources, network platforms and teaching activities (classroom learning and evaluation). The theoretical and practical test scores of the two groups of interns were compared, and the evaluations of the students in the research group on the effect of online and offline mixed teaching were collected. Excel 2013 was used to sort out the data, and R software was used for data processing and statistical analysis. T-test was used for measurement data and Chi-square test was used for counting data. Results:The operational test scores [(28.16±1.70) points] and theoretical scores [(82.07±6.40) points] of the students in the study group were higher than those in the control group [(23.35±2.88) points and (76.20±5.67) points], with significant differences ( P<0.001). Compared with the students in the control group, the students in the research group were more satisfied with the mixed teaching method. Conclusion:The online and offline mixed teaching is conducive to improving students' comprehensive performance, learning effect, and promoting students' clinical diagnosis and treatment skills, self-study, innovation abilities and clinical competence.

Objective : To investigate the effect and mechanism of Urolithin B ( UB) on proliferation , migration , invasion , apoptosis and cell cycle of glioblastoma cells. Methods : The effects of UB on the proliferation , migration and invasion of glioblastoma U251 cells were detected by CCK⁃8 , clone formation assay , scratch healing assay , Transwell invasion assay respectively. The regulation effect of UB on cell cycle and apoptosis was detected by flow cytometry. Western blot was used to detect the effects of UB on the phosphorylation levels of downstream signaling pathway proteins ERK , AKT , p38 and JNK. Results : Compared with the control group , at 24 h and 48 h , the absorbance value of U251 cells was decreased by UB (P < 0. 01) in a dose dependent manner. UB reduced the percentage of cell clone formation (P < 0. 01) . The percentage of the scratch healing area was reduced by UB (P < 0. 05 or P < 0. 01) . The percentage of the number of invaded cells was reduced by UB (P < 0. 01) . UB could induce apoptosis (P < 0. 01) and cause the cells to stagnate in G2/M phase (P < 0. 01) . UB could significantly inhibit the phosphorylation of ERK (P < 0. 05 or P < 0. 01) and AKT (P < 0. 05 or P < 0. 01) . Conclusion UB can inhibit proliferation , migration , invasion , apoptosis and cell cycle of glioblastoma cells , and regulate the phosphorylation levels of ERK and AKT.

Objective:To investigate the clinical manifestations and imaging features of spastic paraplegia caused by spinal cord Wallerian degeneration after pontine infarction, and to analyze its occurrence process and mechanism.Methods:The clinical manifestations and imaging features of two patients with spastic paraplegia caused by spinal cord Wallerian degeneration after pontine infarction were reported for the first time in China. Combined with anatomy and review of the literature, the mechanism, imaging manifestations and clinical features of Wallerian degeneration of lateral funiculus of spinal cord after pontine infarction were analyzed systematically.Results:Case 1 was a 65 years old female, and case 2 was a 58 years old male, who were treated in Qilu Hospital of Shandong University on December 7, 2018 and June 23, 2019 respectively. All the two patients presented with strength weakness of both limbs, hypertonia, symmetric hyperreflexia, and bilateral extensor plantar responses, which suggested spastic paraplegia secondary to upper motor neuron involvement. Spastic paraplegia appeared eight months after pontine infarction in case 1 and appeared six months after pontine infarction in case 2. Magnetic resonance imaging revealed continuous iso-T 1 and high-T 2 signals of bilateral pyramidal tracts below the pontine foci. Case 1 showed lesions of lateral cord of medulla oblongata, cervical spinal cord and thoracic spinal cord, and case 2 showed lesions of lateral cord of medulla oblongata and cervical spinal cord. At the same time, motor neuron disease and metabolic disease were excluded by electromyography and laboratory examination, inflammatory demyelinating disease was excluded by cerebrospinal fluid examination in one case. The syndromes, in combination with a continuous strip of abnormal signal revealed by magnetic resonance imaging which was consistent with the pyramidal tract and connected with the primary lesion suggested wallerian degeneration of spinal cord secondary to pontine infarction. The clinical symptoms of two cases were gradually aggravated in follow-up. Conclusions:Spinal cord Wallerian degeneration is a sequel after pontine infarction, which is related to the prognosis of the disease. A full understanding of its clinical manifestations and imaging features can avoid clinical misdiagnosis as other diseases.

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 prevalence and relevant influencing factors of gynecological diseases of grassroot level female medical staffs. METHODS: A total of 2 308 female medical workers from county, town and village in hengxian County of Guangxi Zhuang Autonomous Region were selected as study subjects by cluster sampling method. The basic information, occupational history, reproductive health and fertility of these subjects were investigated by Reproducetive Health Survey Questionnaine of Female Workers. RESULTS: The total prevalence of gynecological diseases in female medical staffs was 21.6%. Among them, the prevalence of genital tract infections was 15.6%, and gynecological tumors was 6.0%. The top three gynecologic diseases were vaginitis(9.2%), uterine fibroids(4.3%) and cervicitis(3.5%). Multivariate logistic regression analysis results indicated that the younger the patients, the higher the risk of reproductive tract infectious diseases(P<0.01), and the lower the risk of gynecological tumors(P<0.01). The risk of reproductive tract infectious diseases and gynecological tumors in married patients was higher than that in unmarried staffs(P<0.05). The higher the number of abortions, the higher the risk of reproductive tract infectious diseases and gynecological tumors(P<0.01). The risk of reproductive tract infectious diseases was higher and the risk of gynecological tumors was lower in female shift workers than that of non-shift workers(P<0.05). CONCLUSION: Vaginitis, uterine fibroids and cervicitis are the main gynecological diseases in grassroot level female medical staffs. The incidence of gynecological diseases is related to age, history of marriage, childbirth and abortion, and work-shifts.