Progressive dementia is described as the first and most prominent symptom of Alzheimer's disease (AD), and hyperphosphorylation of microtubule associated Tau protein (MAPT) plays a key role in neurodegeneration and neuronal dysfunction in AD and other neurodegenerative diseases. This paper reviews several protein kinases and phosphatases which can phosphorylate/dephosphorylate Tau protein, and evaluates a therapeutic strategy based on targeted inhibition of Tau kinases and activation of Tau phosphatases.
Alzheimer Disease ; metabolism ; physiopathology ; Glycogen Synthase Kinase 3 ; antagonists & inhibitors ; metabolism ; Humans ; Neurodegenerative Diseases ; metabolism ; physiopathology ; Phosphoric Monoester Hydrolases ; metabolism ; Phosphorylation ; Protein Kinases ; metabolism ; tau Proteins ; chemistry ; metabolism ; physiology

Objective To observe the serum vascular endothelial growth factor (VEGF),apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR).Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study.Vision,slit lamp microscope,indirect ophthalmoscope and FFA examinations were performed on all the subjects.According to the results of the examinations combined with the DR clinical staging criteria,the patients were divided into non-DR (NDR) group,non-proliferative DR (NPDR) group,and proliferative DR (PDR) group,with 72,76 and 60 patients in each,respectively.The clinical data of each group were recorded,and the levels of fasting blood glucose (FPG),HbA1c,total cholesterol (TC),three acylglycerol (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C),VEGF,apelin and HO-1 were detected in each group.The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF,apelin and HO-1 in predicting the occurrence of PDR.Correlation analysis of serum VEGF,Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis.Results The level of VEGF (56.82± 10.16 vs 91.74±22.83,140.15±36.40,195.28±42.26 pg/ml)and apelin (2.95±0.53 vs 4.68±0.74,7.25±1.13,10.16± 1.35 ng/ml) in PDR group were significantly higher than those in NPDR,NDR and control groups (F=17.306,21.814;P＜0.05).The level of HO-1 (50.37±10.14 vs 43.58±8.16,30.25t6.28,22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR,NDR and control groups (F=15.827,P＜0.05).The ROC curve analysis showed that the best cut-offvalues of serum VEGF,apelin and HO-1 were 162.50 pg/ml,8.30 ng/ml,27.13 mmol/L,and the three combined to predict PDR of AUC (95％CI)was 0.906 (0.849-0.962),and their sensitivity (90.3％) and specificity (83％) were better.The correlation analysis showed that the VEGF,apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382,0.416,-0.36;P＜0.05),FPG (r=0.438,0.460,-0.397;P＜0.05) and HbAlc (r=0.375,0.478,-0.405;P＜0.05),and the serum VEGF were correlated with apelin and HO-1 (r=0.793,-0.594;P＜0.01).Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR,and the three combination helps predict the occurrence of PDR.

Objective:To explore the differences in dynamic spontaneous brain activity in individuals with subjective cognitive decline (SCD) and its correlation with spatial navigation ability in SCD subjects.Methods:A total of 72 SCD subjects(SCD group) and 67 normal controls (NC group) matched for age, gender and education level were recruited from September 2020 to February 2023 at the Affiliated Drum Tower Hospital, Medical School of Nanjing University. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) examinations, spatial navigation tests and cognitive function assessments. The rs-fMRI time series were segmented using a sliding time window method, and statistical analyses were carried out using SPSS 26.0 software to compare the differences in the dynamic amplitude of low frequency fluctuation (dALFF) between the two groups. Correlation analysis was conducted between dALFF values in different brain regions and scale scores and spatial navigation tests.Results:Compared with the NC group, the dALFF variability in the right precuneus(0.119±0.021, 0.130±0.031) and left cuneus(0.143±0.034, 0.156±0.032) in SCD group decreased ( t=-3.41, -3.12, P<0.05, FDR corrected), and the dALFF variability in the right middle occipital gyrus(0.146±0.023, 0.137±0.020) and right angular gyrus(0.148±0.025, 0.139±0.026) increased ( t=4.51, 3.36, both P<0.05, FDR corrected). The temporal variability of dALFF in the right precuneus in SCD group was negatively correlated with egocentric spatial navigation ( r=-0.341, P=0.025), delayed allocentric spatial navigation ( r=-0.286, P=0.035) and memory function ( r=-0.332, P=0.009). The temporal variability of dALFF in the left middle occipital gyrus was positively correlated with language function ( r=0.339, P=0.015) and visuospatial function ( r=0.343, P=0.008) in SCD group. Conclusions:The temporal variability of dALFF in the right precuneus and the left middle occipital gyrus may be the neurobiological basis of cognitive decline and spatial navigation impairment in SCD subjects, and it can be used as a potential imaging marker for early identification of SCD patients.

Objective: To analyze the diagnostic value of ultrasound guided 14 gauge coreneedle biopsy (US-CNB) in breast nodules. Methods: We retrospectively analyzed the pathological results of US-CNB and surgical excision from 373 breast nodules in Peking University International Hospital from Sep 2016 to Nov 2018 to evaluate the accuracy of 14g US-CNB. Results: A total of 349 patients(373 nodules)underwent US-CNB. US-CNB reported 282 benign lesions(75.6%, 282/373), 20 high-risklesions(5.4%, 20/373), and 71 malignant lesions(19.0%, 71/373). For 282 CNB reported benign lesions, the surgical pathology confirmed 235 lesions , 46 for high-risk lesions and 1 for malignant lesion with a concordancy of 83.3%(235/282)and the underestimation rate was 16.7%(47/282). US-CNB identified 20 high-risk lesions. According to surgical results, 15 were high-risk lesions and 5 were malignant lesions with a concordancy of 75% (15/20)and the underestimation rate was 25%(5/20). When it comes to malignant lesions, the excision results showed that 70 were malignant lesions and 1was high-risk lesion with a concordancy of 98.6%(70/71)and the overestimation rate was 1.4%(1/71). The concordance of the histological type , calculated for 50 invasive carcinomas, was 92% (46/50) with a kappa value of 0.77.The concordance of the histological grade could be calculated for 38 invasive ductal carcinomas with the Elston-Elllis Method . It was 89.5% (34/38) with a kappa value of 0.57. Conclusions The pathology result of 14gUS-CNB is in good consistency with surgical excision for breast benign and malignant lesions.