Purpose To explore the value of the new generation tau PET tracer 18F-Florzolotau in Alzheimer's disease(AD)at different stages.Materials and Methods Twenty-five MCI patients and sixty-one AD patients with positive β-amyloid status in Huashan Hospital,Fudan University from February 2020 to January 2022 were retrospectively enrolled with 18F-Florzolotau PET imaging and demographic and clinical data.The pre-processed PET images were analyzed by SPM two-sample t-test between MCI and AD groups,and the standardized uptake value ratios(SUVR)were extracted from the region of interest defined by SPM analysis(P＜0.001);scaled subprofile model/principal component analysis was used to construct the different tau related patterns(MCItauRP,ADtauRP)and calculate the corresponding expression values.The classification efficiency of SUVR and MCItauRP,ADtauRP expression values was evaluated by receiver operating characteristic curve.Results Compared with MCI patients,tau protein deposition of AD patients was increased mainly in the bilateral temporal,occipital lobe(P＜0.001),and the SUVR of these brain region in the AD group was higher than that in the MCI group(Z=-3.164,P＜0.00l);the expression values of MCItauRP and ADtauRP were significantly different between the AD group and MCI group(t=3.72,Z=-3.51;both P＜0.001),and these expression values of AD patients were higher than those in the MCI group;the accuracy of tauRP expression values and SUVR for the differentiation between the AD and MCI group were 61.63％,65.12％and 65.12％,respectively;the sensitivity was 88.00％,96.00％and 100.00％,respectively;the specificity was 50.82％,52.46％and 50.82％,respectively.Conclusion The new tau PET can identify and distinguish the differences in tau protein deposition between AD and MCI patients.However,the classification and diagnosis efficiency is not high.In the future,it is necessary to find a more ideal analysis method.

Objective:To compare the localization accuracy of interictal 18F-FDG and 18F-flumazenil (FMZ) PET/CT imaging for focal cortical dysplasia (FCD). Methods:A retrospective analysis was conducted on 22 patients (12 males, 10 females; age 8-36 years) with pathologically confirmed FCD who underwent surgical resection at Huashan Hospital, Fudan University from July 2021 to June 2023. All patients underwent 18F-FDG and 18F-FMZ PET/CT scans before surgery. Surgical pathological diagnosis was used as the gold standard. Visual scoring was used to analyze the images. The accuracy of the two imaging methods in the localization of FCD was compared, and subgroup analysis (FCD Ⅱa, FCD Ⅱb) of different pathological type was further performed. Paired- t test, χ2 test or Fisher′s exact test was used to analyze the data. Results:The visual score of 18F-FMZ PET/CT was higher than that of 18F-FDG (3.00±0.82 vs 2.27±0.92; t=4.17, P=0.020). The accuracy of interictal 18F-FMZ PET/CT was 77.27%(17/22), which was higher than that of 18F-FDG PET/CT (36.36%, 8/22; χ2=7.50, P=0.006). Subgroup analysis showed that within the cohort of patients diagnosed with FCD Ⅱa ( n=18), 18F-FMZ PET/CT outperformed 18F-FDG in terms of accuracy for localization (15/18 vs 6/18; P=0.006). Conclusion:Compared to 18F-FDG, 18F-FMZ PET/CT demonstrates clearer and more accurate identification of lesion borders, and exhibits higher precision, which provides valuable guidance for preoperative localization.

Objective:To investigate characteristics and differences of cerebral glucose metabolism in patients with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis from the perspective of different trigger factors of antibodies. Methods:A total of 15 patients (8 males, 7 females, age (30.5±17.7) years) with anti-NMDAR encephalitis between January 2016 and January 2019 in Huashan Hospital, Fudan University were recruited retrospectively. All patients underwent resting state cerebral 18F-FDG PET imaging. The characteristics of brain glucose metabolism were analyzed, and the SUV ratio (SUVR) was semi-quantitatively compared with that in 12 healthy subjects (HS; 7 males, 5 females, age (51.5±9.6) years). Independent-sample t test was used to analyze the data. Results:Among 15 patients, 5 patients were viral encephalitis-related anti-NMDAR encephalitis, showing focal decreased metabolism in unilateral temporal lobe or basal ganglia (SUVR: patients: 0.659±0.219; HS: 1.754±0.203; t=-9.58, P<0.001), with increased metabolism in contralateral temporal lobe or basal ganglia (SUVR: patients: 2.275±0.244; HS: 1.960±0.227; t=2.55, P=0.022) in 18F-FDG PET imaging. Six patients were cryptogenic anti-NMDAR encephalitis, showing asymmetric increased metabolism in frontal, temporal, parietal and basal ganglia (SUVR: patients: 2.482±0.395; HS: 1.754±0.203; t=5.23, P<0.001), with decreased metabolism in bilateral occipital lobes. The remaining 4 cases were paraneoplastic origin accompanied by teratoma, showing increased metabolism in bilateral temporal and basal ganglia (SUVR: patient: 2.359±0.181; HS: 1.960±0.227; t=3.16, P=0.007), with mild decreased metabolism in bilateral occipital lobe. Conclusions:The abnormal changes of cerebral glucose metabolism in patients with anti-NMDAR encephalitis can be divided into at least three patterns according to different trigger factors. A comprehensive understanding of these characteristic metabolic changes is helpful for detecting disease, and may provide potential value in indicating different causes.

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.

Objective:To reveal the abnormal topology of brain network in Alzheimer′s disease (AD), and evaluate the laterality of tau protein deposition in brains of AD patients based on 18F-APN-1607 PET brain imaging combined with graph theory. Methods:From November 2018 to January 2020, 23 clinically diagnosed AD patients (9 males, 14 females; age (61.3±10.7) years) and 13 normal controls (NC) (9 males, 4 females; age (61.6±4.5) years) who underwent 18F-APN-1607 PET imaging in Huashan Hospital, Fudan University were analyzed in this cross-sectional study. The brain network analysis method based on graph theory was used to construct the tau network of the NC group and the AD group, the network attributes (clustering coefficient, shortest path length, local efficiency, and small-worldness) were calculated, and the asymmetry index (AI) of each group to evaluate the laterality of tau protein deposition was obtained. Permutation test (1 000 times) was used to analyze the differences in brain network parameters between the NC group and the AD group. Results:The tau network of the AD group had obvious topological disorder, and the connections in the olfactory cortex and temporal lobe were weakened, while in the posterior cingulate gyrus, anterior wedge, and parietal occipital lobe, the connections were enhanced. Compared with NC group, clustering coefficient ( t values: 2.28-2.69), local efficiency ( t values: 2.34-3.06) and small-worldness ( t values: 2.26-3.32) were significantly decreased in AD group (all P<0.05) with the sparsity of 20%-50%, while the shortest path length was significantly increased ( t values: 2.13-2.85; all P<0.05). There was significant tau laterality in the posterior cingulate gyrus, superior parietal gyrus, paracentral lobule, superior temporal gyrus and middle temporal gyrus (AI: 10.5%(8.1%, 13.9%), 14.1%(7.6%, 20.3%), -12.4%(-15.7%, -7.8%), -10.8%(-15.3%, -2.1%) , -12.1%(-17.9%, -6.6%), respectively). Conclusion:The tau network analysis based on 18F-APN-1607 may be used to reveal abnormal topological changes of AD patients, and the tau deposition in the posterior cingulate gyrus, superior parietal gyrus, paracentral lobule, superior temporal gyrus and middle temporal gyrus has obvious laterality in AD patients.

Objective:Exploring tau related disease pattern (tauRDP) in the brain of Alzheimer′s disease (AD) patients based on 18F-APN-1607 PET scan. Methods:18F-APN-1607 PET images were collected from 17 AD patients (6 males and 11 females, age: (61.7±12.3) years, Mini-Mental State Examination (MMSE) score: 17.6±7.9) and 10 normal controls (NC; 6 males and 4 females, age: (61.2±4.7) years) from Huashan Hospital of Fudan University. The scaled subprofile model (SSM) based on principal component analysis (PCA) technique was used to construct the tauRDP. Then the expression value of tauRDP in each sample was calculated. The differences on tauRDP expression values between AD patients and NC were compared by independent-sample t test. Pearson correlation analysis was used to analyze the correlation between tauRDP expression values and MMSE values in AD patients. Results:The tauRDP area mainly included: precentral gyrus, dorsolateral superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus of opercular part, inferior frontal gyrus of triangular part, supplementary motor area, medial superior frontal gyrus, left median cingulate and paracingulate gyri, right cuneus, superior occipital gyrus, middle occipital gyrus, postcentral gyrus, superior parietal gyrus inferior parietal, but supramarginal and angular gyri, supramarginal gyrus, angular gyrus, precuneus and middle temporal gyrus. There were significant differences ( t=4.395, P<0.001) between AD group (12.6±8.0) and NC group (0.0±1.0) in tauRDP expression values. The tauRDP expression values were correlated with MMSE values in AD group significantly ( r=-0.566, P=0.018). Conclusions:TauRDP established basing on SSM/PCA method can be used to quantitatively express the abnormal spatial distributions of tau deposition. Expression value of tauRDP has the potential to initially assess the severity of AD.

Ascorbic Acid ; chemistry ; pharmacology ; Cellular Reprogramming ; Genetic Vectors ; genetics ; metabolism ; Histone Deacetylases ; genetics ; metabolism ; Humans ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; Protein Kinase Inhibitors ; chemistry ; pharmacology ; RNA, Small Interfering ; metabolism

Objective To investigate the differentiation of neuroendocrine component (NEC) in colorectal adenocarcinoma in relation to its significance by comparing the outcome between patients with or without NEC.Methods The paraffin sections from patients with pathologically confirmed colorectal adenocarcinoma were retrospectively collected and screened for those with NEC by morphological examination and immunohistochemistry with neuroendocrine markers.Control patients (n=54) without NEC were selected from colorectal cancer database and 2: 1 matched on the basis of clinical features with NEC positive patients (n=27).Relative analysis was performed between two groups.Results With a median follow-up of 72 months,the 5-year disease free survival was 58.0% (16/27) in NEC positive group and 79.1% (43/54) in control group (P=0.036).Similarly,the 5-year cancer-specific overall survival was significantly lower in NEC positive group than in control group (58.3% versus 81.1%,P=0.037).Cox regression showed that the 5-year cumulative risks of disease recurrence and cancer-caused death in NEC positive patients were 2.38 and 2.41 times higher than those in control patients,respectively.Conclusions NEC appears to bear a poor prognosis in patients with colorectal adenocarcinoma.

By using ATP-ase histochemical and OKT6 colloidal goldsilver immunohi- stochemical methods, we have studied the location and distribution of Langer- han's cells (LCs) in human esophageal epithelium. The results of our study showed that the dendritic LCs scatter in the basal and middle layers of the esophageal epithelium. The morphology and density of LCs are variable as the age grows and the location changes, more LCs are found in the adult esophageal epithelium than in the foetus, and more LCs are found in the lower segment of esophagus than in the upper segment.