G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.

Objective:To standardize the quantitation of 18F-Florbetapir PET SUV ratio (SUVR) to the Centiloid (CL) scale, and analyze the positive rate of β-amyloid (Aβ) in Chinese Preclinical Alzheimer′s Disease (AD) Study (C-PAS). Methods:11C-Pittsburgh compound B(PIB) and 18F-Florbetapir images from public databases " Standard PIB" and " Florbetapir Calibration" were preprocessed by statistical parametric mapping (SPM) 12, and the transformative formulas from SUVR to CL were derived. Then a total of 942 subjects (357 males, 585 females; age (66.4±8.1) years) from C-PAS who received 18F-Florbetapir PET at the Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University from October 2018 to August 2023 were retrospectively included. CL values were calculated and the Aβ positive rates (CL value≤12, Aβ negative; 12< CL value<30, Aβ subtle pathology; CL value≥30, Aβ positive) of AD, mild cognitive impairment (MCI) and cognitive unimpaired (CU) groups were explored. Data were analyzed by using Kruskal-Wallis rank sum test, Dunn′s test (Bonferroni correction ) and χ2 test. Results:The formula for the 18F-Florbetapir SUVR converted to CL was CL=179.64×SUVR_Florbetapir-186.95. In the C-PAS cohort, the SUVR, CL value, Aβ positive rate (including subtle pathology) of patients with clinically diagnosed AD were 1.29±0.22, 43.97±39.23, 71.80%(140/195), which were 1.04(1.02, 1.14), 1.16(-4.04, 17.14), 28.50%(61/214) for patients with MCI, and 1.04(1.01, 1.08), 0.54(-5.29, 7.69), 15.38%(82/533) for CU subjects, respectively. SUVR, CL value and the ratio of negative, subtle and positive Aβ pathology of the above three groups exhibited statistical differences ( H=148.30, H=148.30, χ2=262.12, all P<0.001). Besides, mixed MCI group exhibited higher CL values ((2.45(-1.54, 46.32) vs -1.58(-6.33, 7.20); H=8.21, P=0.016; z=2.81, P=0.015) and Aβ positive rate (including subtle pathology) (41.18%(14/34) vs 14.64%(6/41); χ2 values: 12.71 and 10.63, both P<0.01), compared to non-amnestic MCI group. The CL values and Aβ positive rates were also increased with age in CU group. Conclusion:This study validates the feasibility of the CL formula with 18F-Florbetapir images and reveals Aβ deposition in C-PAS cohort, which can lay the foundation for multi-center Aβ PET studies in China.

Objective:To investigate the application of (4R)-4-(3-[ 18F]fluoranyl-5-fluorophenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one( 18F-SynVesT-1), a synaptic vesicle glycoprotein 2A (SV2A) radioactive tracer, in patients with Alzheimer′s disease (AD). Methods:A total of 20 AD patients (2 males, 18 females, age (66.4±8.1) years) with positive β-amyloid (Aβ) deposition and 20 normal controls (NC; 9 males, 11 females, age (62.6±8.6) years ) without Aβ deposition were retrospectively recruited from Huashan Hospital, Fudan University between December 2021 and December 2022. All of them underwent 18F-SynVesT-1 PET/MR and 18F-Florbetapir (AV45) PET/CT scans. Preprocessing of brain 18F-SynVesT-1 PET images was carried out using statistical parametric mapping (SPM). The differences of the uptke of 18F-SynVesT-1 (synaptic density) between two groups based on ROI were compared by using either the independent-sample t test or Mann-Whitney U test. Spearman rank correlation analysis was performed to assess the relationship between synaptic density and cognitive performance. For voxelwise analysis, a general linear model was constructed to analyze differences in synaptic density between the two groups using the independent-sample t test. Furthermore, a multiple linear regression model was developed to explore the relationship between synaptic density and cognitive performance. Results:Compared to the NC group, the AD group exhibited significant widespread reduction in synaptic density across the cortical regions ( P<0.05, false discovery rate (FDR)-corrected), particularly in the medial temporal lobe (0.84±0.09 vs 1.04±0.09; t=-6.95, P<0.001), lateral temporal lobe (1.15±0.13 vs 1.31±0.08; t=-4.56, P<0.001), and lateral parietal lobe (1.24(1.04, 1.26) vs 1.32(1.23, 1.39); z=-3.25, P=0.001). Moreover, synaptic density in extensive cortical regions showed a positive correlation with mini-mental state examination (MMSE) and Montreal cognitive assessment-basic (MoCA-B) scores ( P<0.05, FDR-corrected). Notably, significant associations were observed between MMSE and MoCA-B scores and synaptic density in the lateral temporal lobe ( rs values: 0.71, 0.74, both P<0.001) and medial temporal lobe ( rs values: 0.71, 0.74, both P<0.001). Conclusions:18F-SynVesT-1 PET imaging is a valuable tool for evaluating synaptic density, specifically in the context of AD. The observed widespread reduction in synaptic density across cortical regions of patients with AD are closely related to cognitive decline.

Alzheimer's disease (AD) is the most common cause of cognitive impairment. Beyond clinical diagnosis, AD pathologic changes are considered as "gold standard" for mechanistic research or new drug development studies. According to AD research framework, neurodegeneration occurs after amyloid-β and Tau protein deposition and before cognitive decline. Due to lower-and medium-field MRI limitation, most of these neurodegenerative characteristics identified at present appear at middle or late stage of AD, hardly being an early warning signal. 7T MRI system, representing the most advanced field strength MRI presently, is characterized by its exceptional resolution and sensitivity that facilitate the early identification of neurodegeneration. This article reviews the recent advance in 7T MRI in AD spectrum and brain structures associated with AD, aiming to enhance the utilization of 7T MRI in this field.

Objective: The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. Materials and Methods: Forty-nine women with preeclampsia (mean age 32.4 years; range, 18–44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23–40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20–42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. Results: Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361–0.812). Conclusion Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

Behavioral and psychological symptoms of dementia (BPSD) is a common symptom of Alzheimer's disease (AD), with an occurrence of 90%. BPSD can lead to poor prognosis and dysfunction in patients with AD, but few safe and effective treatments are available. This article overviews the occurrence frequencies of different manifestations of BPSD in AD and their changes with clinical courses of the disease, and introduces the current research progress on genetic characteristics, pathophysiological mechanism, biomarkers and therapeutics of BPSD in AD to provide references for early recognition and treatment of BPSD in AD.

Objective:To investigate the tau deposition pattern in Alzheimer′s disease (AD) and its correlation with cognition by 18F-MK6240 PET imaging. Methods:From August 2021 to February 2022, 46 elderly people over 55 years old (16 males, 30 females; age (68.9±7.7) years) were included from outpatient and community in Shanghai. Structural brain MRI, β-amyloid (Aβ) PET imaging, tau-PET imaging and comprehensive neuropsychological tests batteries were conducted. The subjects were divided into AD group ( n=16) and normal cognition (NC) group ( n=30) according to the 2018 National Institute on aging and Alzheimer′s Association (NIA-AA) diagnostic criteria. Quantitative analysis was conducted to investigate the tau deposition pattern in AD after preprocessing 18F-MK6240 PET images with MRI images. SUV ratio (SUVR) of brain regions such as entorhinal cortex, hippocampus, parahippocampal gyrus, amygdala, insular lobe, frontal lobe, precuneus, occipital lobe, thalamus and putamen were analyzed, with cerebellum as reference region. The differences of tau deposition in brain regions between AD and NC groups were analyzed by independent-sample t test. The associations between SUVR and Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment-Basic (MoCA-B) score were analyzed by Pearson correlation analysis. Results:AD displayed a significant tau deposition in frontal lobes, temporal lobes and parietal lobes compared with NC. SUVR of brain regions in AD group were higher than those in NC group ( t values: 3.37-9.61, all P<0.05). SUVR in brain regions were negatively correlated with MMSE score ( r values: from -0.735 to -0.350, all P<0.05) and MoCA-B score ( r values: from -0.723 to -0.367, all P<0.05). Conclusion:18F-MK6240 PET can demonstrate the tau deposition in the brain of AD patients, and the tau deposition is related to cognitive function.

Objective To analyze the equity of the allocation of oral medical resources and the accessibility of health service capabilities in Wuhan. Methods The equity of oral medical resources was calculated with Gini coefficient and Theil index, accessibility was assessed by two-step floating catchment area model, and the spatial autocorrelation was used to study the high-low clustering of accessibility. Results The Gini coefficient of oral medical resources based on population level was around 0.3, and the Gini coefficient of oral medical resources based on geographic area was greater than 0.6. Theil index calculation results were similar. In terms of overall accessibility, the area with poor accessibility was 2,428 square kilometers, reaching 28.38% of the total area, while the area with better accessibility accounted for 14.18%. Conclusion The allocation of oral medical care resources based on population distribution was fairer and better than that based on geographic area. Moreover, the geographical accessibility varies greatly between regions, showing the characteristics of high-high cluster and low-low cluster.