Objective:To explore the characteristics of self-referential network (SRN) functional connectivity in subjective cognitive decline (SCD) patients with normal and impaired metacognition.Methods:Seventy-one subjects were selected from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 25 cognitively normal controls and 46 SCD patients. The metacognitive level of SCD patients was assessed by Everyday Cognition Scale (ECog), and then, they were divided into a metacognitively normal group ( n=25, metacognitive scores>-0.074) and a metacognitively impaired group ( n=21, metacognitive scores≤-0.074). Results of Geriatric Depression Scale (GDS), Montreal Cognitive Scale (MoCA), Mini‐Mental State Examination (MMSE), Rey Auditory Word Learning Test (RAVLT), Logical Memory Scale, expressions of pathological markers (cerebrospinal fluid β-amyloid protein [Aβ], total tau protein [t-tau] and phosphorylated tau protein [p-tau]), brain glucose metabolism, and functional magnetic resonance imaging (fMRI) were collected and compared among the 3 groups. Independent component analysis (ICA) was used to extract SRN and analyze the different brain regions among the 3 groups; Pearson correlation was used to analyze the correlations of SRN functional connectivity changes with cognitive scales and pathological markers. Results:No significant differences in demographic characteristics (age and gender), scores of GDS, MoCA and MMSE, or levels of Aβ, t-tau, p-tau and brain glucose metabolism were noted among the 3 groups ( P>0.05). The metacognitive scores in metacognitively impaired group were significantly lower than those in metacognitively normal group and cognitively normal controls ( P<0.05). Significant difference in the functional connectivity of bilateral anterior cingulate gyrus and bilateral orbitofrontal cortex was noted among the 3 groups (TFCE-FWE correction, P<0.01, voxel>100); compared with the cognitively normal controls, the metacognitively impaired group showed significantly decreased functional connectivity of bilateral orbitofrontal cortex, while the metacognitively normal group showed enhanced functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100); compared with the metacognitively normal group, the metacognitively impaired group had statistically decreased functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100). Further correlation analysis showed that difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and cognitively normal controls was negatively correlated with RAVLT-immediate scores ( r=-0.445, P=0.043); difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and metacognitively normal group was negatively correlated with RAVLT-immediate scores ( r=-0.463, P=0.034). Conclusion:SCD patients with different metacognitive levels have characteristic SRN functional connectivity changes; impaired metacognition may be an early feature of Alzheimer's disease.

Objective:To investigate the protective effect and potential mechanisms of microRNA-26a-5p (miR-26a-5p) on podocyte injury in diabetic kidney disease (DKD).Methods:(1) In vivo experiment: Four-week-old db/db mice were divided into db/db group, db/db+agomir-NC group and db/db+miR-26a-5p agomir group according to random number table method, with 10 mice in each group, and 10 db/m mice of the same week-old were set as normal control group. At the age of 10 weeks, pathological changes were observed through light and electron microscopy. Kidney weight/body weight (KW/BW), urinary albumin to creatinine ratio (ACR), fasting blood glucose (FBG) and other biochemical indicators were also detected. The position and expression of miR-26a-5p in kidney tissue were determined through fluorescence in situ hybridization and quantitative real-time PCR, while the expressions of transient receptor potential cation channel-6 (TRPC6) and Nephrin in kidney tissue were determined by Western blotting and immunohistochemistry. (2) In vitro experiment: The immortalized mouse podocytes (MPC5) were divided into 5 groups: normal glucose group, high mannitol group, high glucose group, high glucose+miR-26a-5p mimic group, and high glucose+mimic-NC group. The expressions of miR-26a-5p, TRPC6 and Nephrin were detected. Luciferase reporter assay was conducted to research the relationship of miR-26a-5p and TRPC6. Results:(1) In vivo experiment: Compared with db/m group, db/db mice exhibited lower KW/BW and disrupted conditions of ACR, FBG, total cholesterol, triglycerides and low density lipoprotein cholesterol (all P<0.01). Increased glomeruli volume, more extracellular matrix deposition, thicker basement membrane and more foot process fusion were observed by light and electron microscope. Increased expression of TRPC6 protein as well as decreased expression of Nephrin protein and miR-26a-5p were detected in kidney tissues of db/db mice ( P<0.05). Compared with db/db+agomir-NC group, db/db mice transfected by miR-26a-5p agomir exhibited less albuminuria, with less protein expression of TRPC6 and more Nephrin in kidney tissue (all P<0.05). (2) In vitro experiment: Compared with normal glucose group, high glucose-treated podocytes exhibited increased expression of TRPC6 ( P<0.05), as well as decreased expression of Nephrin ( P<0.05) and miR-26a-5p ( P<0.01). Compared with high glucose+mimic-NC group, lower expression of TRPC6 and higher expression of Nephrin were detected in podocytes transfected by miR-26a-5p mimic (both P<0.05). Luciferase reporter assay confirmed that miR-26a-5p could regulate the expression of TRPC6 precisely. Conclusions:The expression of miR-26a-5p in podocytes is down-regulated in the context of high glucose and miR-26a-5p protects podocytes from injury via inhibiting the expression of TRPC6 in DKD.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

By reviewing the organization and implementation of “Hongsha-2021” Guangxi nuclear emergency joint exercises, this article summarizes the experience in the organization process and puts forward some thoughts and suggestions in order to improve the depth of provincial-level on-site and off-site joint exercises for nuclear emergency at nuclear power plants and further enhance the emergency response capacity of nuclear emergency organizations at all levels.

Objective:To investigate the function of glutamatergic neuron of the parasubiculum in spatial memory.Methods:Sixteen adult male C57BL/6 mice aged 6-8 weeks were divided into two groups randomly, 0.4 μl AAV5-CaMKⅡα-eNpHR3.0-eYFP was injected into the bilateral parasubiculum respectively in experimental group, equal dose AAV5-CaMKⅡα-eYFP for control group.The optic fiber was implanted 6 weeks after virus injection.The novel object place recognition test was performed one week after optic fiber implantation, continuous yellow light was delivered during the behavioral test to inhibit the function of glutamatergic neuron in the parasubiculum.The standard memory index (D2) was used to evaluate the spatial memory function.SPSS 20.0 software was used to process the data, and the independent-samples t-test and paired-samples t-test were used for data analysis. Results:In the novel object place recognition experiment, the mice showed no preference for either object in both control group(new object: 0.51±0.06, familiar object: 0.49±0.04, t=1.21, P>0.05) and experimental group(new object: 0.49±0.05, familiar object: 0.50±0.04, t=-0.78, P>0.05). Compared with the control group (0.55±0.06), the D2 score of the experimental group (0.26±0.07) was significantly lower ( t=-2.96, P<0.05), and the number of c-fos positive neuron in experimental group (96.33±7.13) was also significantly less than that in control group (127.67±5.24, t=-3.54, P<0.05). Conclusion:Inhibiting glutamatergic neuronal activity in the parasubiculum impairs spatial memory in mice, suggesting that glutamatergic neurons of the parasubiculum play an important role in spatial memory.

Objective:To explore the relations of changes in the cognitive function with brain structure network in patients with cerebellar infarction.Methods:Thirty-six patients with cerebellar infarction at the posterior lobe, admitted to our hospital from July 2016 to October 2019, were chosen as cerebellar infarction group; and 30 healthy subjects matched with age, gender, and education level at the same time period were used as control group. Neurocognitive and behavioral tests were performed on both groups to assess the cognitive functions, and MR imaging was performed to obtain diffusion tensor imaging (DTI) data. Deterministic tractography and graph theory were used to obtain the structural brain network and network parameters of all subjects. The differences of clinical data and brain network topological characteristic parameters between the two groups were compared, and the correlation between the subjects' brain structural network characteristic parameters and cognitive function was analyzed.Results:As compared with the control group, patients in the cerebellar infarction group had significantly lower Mini-mental State Examination (MMSE), Montreal Cognitive Scale (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Digit Span Test (DST), Clock Drawing Test (CDT) and Berg Balance Scale (BBS) scores, and significantly longer Trail Making Test (TMT) time-consuming ( P<0.05). As compared with the control group, the cerebellar infarction group showed significantly decreased global efficiency (Eglob) and local efficiency (Eloc) in the brain network, and significantly increased clustering coefficient (Cp) and length of path (Lp, P<0.05). As compared with the control group, the cerebellar infarction group had significantly reduced nodal efficiency in 14 brain regions ( P<0.05), including bilateral median cingulate and paracingulate gyri (DCG), left inferior frontal gyrus-opercular part (IFGoperc), bilateral supplementary motor area (SMA), bilateral precuneus (PCUN), left inferior frontal gyrus-orbital part (ORBinf), left temporal pole-superior temporal gyrus (TPOsup), left temporal pole-middle temporal gyrus(TPOmid), left inferior parietal-supramarginal and angular gyri (IPL), bilateral posterior cingulate gyrus (PCG), left inferior frontal gyrus-triangular part (IFGtriang). MoCA scores were significantly negatively correlated with Lp ( r=-0.388, P=0.019), and were significantly positively correlated with Eglob ( r=0.350, P=0.036), and efficiencies in the right DCG ( r=0.428, P=0.009), left DCG ( r=0.359, P=0.031) and right PCG ( r=0.350, P=0.037) in the cerebellar infarction patients. The RAVLT scores showed a significantly positive correlation with Eglob ( r=0.338, P=0.044). The TMT-A time-consuming and left DCG had significant negative correlation ( r=0.357, P=0.032). TMT-B time-consuming was significantly negatively correlated with right DCG ( r=-0.432, P=0.008), right PCUN ( r=-0.350, P=0.036) and left DCG ( r=-0.398, P=0.016), and positively correlated with Lp ( r=0.406, P=0.014). Conclusions:There is cognitive dysfunction in multiple domains after acute cerebellar infarction, including memory, executive function, visuospatial ability and attention. At the same time, there are reduced efficiency of information transmission in bilateral PCUN, PCG and DCG, and the frontal temporal lobe; among them, the abnormal changes of the right PCG, bilateral DCG, and right PCUN may play key roles in cognitive dysfunction.

The pathogenesis of vascular cognitive impairment (VCI) remains unclear. There is a lack of specific treatment methods, and there is no unified evaluation standard for its clinical efficacy. In recent years, in addition to traditional drug therapy, the role of non-drug therapy in VCI therapy has gradually attracted attention. This article reviews the drug therapy, non-drug therapy and preventive interventions to improve the cognitive symptoms of VCI.

OBJECTIVE: To analyze the characteristics of vestibular migraine (VM), in order to understand the auditory and vestibular function. METHOD: One hundred cases of confirmed or suspected VM patients were observed. Routine examination including pure tone test, vestibular dual temperature test and vestibular evoked myogenic potential(VEMP) and video head impulse test(v-HIT) Were conducted. RESULT: The incidence of male and female was about 1.00 : 2. 57. The average age of onset was 47 years, of which the youngest was 19 years old, and the oldest was 74 years old. Ninty-three cases of patients presented with vestibular sensitive performance, including photophobia, phonophobia,or motion sensitive. Fourty-two patients had migraine at the onset of the disease. Thirty-four patients had cochiear symptoms, including tinnitus, ear fullness, or epicophosis. In seventeen cases of fatigue, tension or poor sleep can cause vertigo. Nine patients had low blood pressure, 7 patients presented with hypertension. Two cases of vertigo were closely related to the change of position, and 1 case had visual aura. In the experiment, 94 patients had undergone VEMP test,with 44 cases of abnormal VEMP value. Seventy-nine patients had been examined v-HIT,of whom 2 patients were abnormal (both of which were reduced). Pure tone audiometry was abnormal in 35 cases. Five cases of patients showed abnormal vestibular-double temperature test. CONCLUSION Vestibular migraine is more prone to female, with young middle age, and can be accompanied by cochlear symptoms. Vestibular function tests (low frequency and high frequency) are normal.
Adult ; Aged ; Audiometry, Pure-Tone ; Evoked Potentials ; Female ; Head Impulse Test ; Humans ; Male ; Middle Aged ; Migraine Disorders ; diagnosis ; Vestibular Function Tests ; Vestibule, Labyrinth ; physiopathology ; Young Adult

This study aims to analyze and improve Howland current source circuit and to study the constant current source of alternating current with high output impedance and high stability. A simulation study was carried out on the constant-current characteristics of Howland current source from two aspects of resistance match value and the selection of Op amp parameters, and then the output impedance was analyzed. The simulation experiment showed that when it was with the best matched resistance, the constant-current characteristics of Howland current source was better. Op amp parameters could affect the constant-current characteristics of Howland current source. In Howland current source circuit, the current source after parameter optimization had better output impedance and load capacity. The results showed that there was the best matched resistance in the selection by Howland current source. The Op amp with large broadband, high slew rate and open loop gain, and wide range of power supply voltage is more suitable for the bioelectrical impedance detection circuit.
Electric Impedance ; Electric Power Supplies ; Electricity

Objective To investigate the relationship between spontaneous hemorrhagic transformation and prognosis after cerebral infarction.Methods Three hundred and thirty-seven cases with acute ischemic stroke at the Brain Hospital Affiliated to Nanjing Medical University from Nov.2011 to Jul.2012 were selected as our subjects.All the relevant clinic and laboratory examination data which influencing spontaneous hemorrhagic transformation were collected.Brain CT or MRI within 3 d after admission or when neurological deficit deterioration happened was performed.Based on brain CT scan or MRI,patients were divided into hemorrhagic transformation(HT) group or non-HT(NHT) group.All cases were followed up for 3 month.Results All of 337 patients,44 cases occurred in spontaneous hemorrhagic transformation,accounting for 13.1％.The mortality rate was 6.8％ (3 cases) in 3 months followed-up at HT group,and the death/disability rate was 47.7％ (21 cases).Meanwhile,the mortality rate was 7.5％ (21 cases) in 3 months followed-up at NHT group,and the death/ disability rate was 35.5％ (104 cases).There was no significant difference between the two groups(x2 =3.10,P =0.376).Multivariate logistic regression analysis demonstrated that age (OR =1.054,95 ％ CI 1.021-1.087),gender(OR =2.131,95％ CI 1.151-3.945) and the national institutes of health stroke scale(OR =1.275,95％ CI 1.174-1.384) were independent predictors of death/dependence at 3 months after ischemic stroke attacked.Conclusion Spontaneous hemorrhagic transformation is not the risk factor of death/dependence on 3 month after symptom onset for ischemic stroke patients.Spontaneous hemorrhagic transformation should be detected as early as possible and adjusted therapy scheme in time,which will help in terms of prognosis.