Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in immune evasion, and analyze its related pathogenic mechanism. Methods:C57BL/6 mice were injected with 10 9 colony-forming unit of wild-type (CFT073 wt) or tcpc gene-knockout (CFT073 Δ tcpc) UPEC CFT073 strains from urethra into bladder to construct a mouse model of pyelonephritis. These mice were sacrificed 5 d after infection and their kidneys were taken to observe the gross pathological changes. Hematoxylin-eosin staining was used to observe histopathological changes in kidney tissues and immunohistochemistry was performed to locate TcpC in kidney tissues. The bacterial loads in urine samples of UPEC infected-mice were counted by ten-fold dilution method, and the presence of tcpc gene in the genomic DNA of bacteria from CFT073-infected mouse kidney or urine samples was measured by PCR. The expression of TcpC at mRNA level was detected by qRT-PCR after infecting dendritic cells with CFT073 wt strains. The influences of UPEC infection on the activation of NF-κB signaling pathway and the secretion of proinflammatory factors by dendritic cells were analyzed by Western blot and ELISA, respectively. The viability of UPEC strains in dendritic cells were observed by laser confocal microscope. Results:Compared with the CFT073 Δ tcpc group, the mice in the CFT073 wt group had obvious abscess in the kidneys as well as massive neutrophil infiltration and abundant TcpC in kidney tissues. The bacterial loads in the urine of CFT073 wt-infected mice were significantly higher than those in the urine of CFT073 Δ tcpc mice. PCR results showed that tcpc gene was successfully amplified from mouse kidney and urine samples. Increased expression of TcpC at both mRNA and protein levels was detected in CFT073 wt-infected dendritic cells. CFT073 wt infection inhibited the phosphorylation of NF-κB p50 and the production of proinflammatory factors in dendritic cells. TcpC promoted the survival of CFT073 wt in dendritic cells. Conclusions:TcpC expression increases significantly during CFT073 wt infection or in mice with CFT073 wt-induced pyelonephritis. It promotes the survival of CFT073 wt in dendritic cells by inhibiting the activation of NF-κB signaling pathway and reducing the secretion of pro-inflammatory cytokines. TcpC is involved in the pathogenesis of UPEC and immune evasion.

Objective:To compare the effects of different reference brain regions on the semi-quantitative SUV ratio (SUVR) of 18F-Florzolotau PET images of Alzheimer′s disease (AD). Methods:The 18F-Florzolotau PET images of 28 (13 males, 15 females, age (57.3±9.5) years) normal controls (NC), 19 patients (4 males, 15 females, age (73.3±7.3) years) with β-amyloid (Aβ)-positive mild cognitive impairment (MCI) and 40 patients (19 males, 21 females, age (61.9±9.1) years) with AD were collected from Huashan Hospital, Fudan University between November 2018 and July 2020. Six semi-quantitative reference brain regions were defined, including whole cerebellum (WC), cerebellar gray matter (GM), cerebellar white matter (WM), parametric estimation of reference signal intensity (PERSI), WC after partial volume correction (WC_pvc), cerebellar GM after partial volume correction (GM_pvc). SUVR was calculated for 14 ROIs, which included the whole brain defined by the automated anatomical labeling (AAL) template, fusiform, inferior temporal, lingual, middle temporal, occipital, parahippocampal, parietal, posterior cingulate, precuneus defined by the AAL template, and Meta ROI composed of the above brain regions, and braak_Ⅰ-Ⅱ, braak_Ⅲ-Ⅳ, braak_Ⅴ-Ⅵ defined by the Desikan Killiany template. AUC was used to evaluate the classification ability of SUVR, and the correlation between SUVR and clinical scale scores were assessed by Spearman rank correlation analysis. Results:The SUVRs of most brain regions showed a steady upward trend in the AD disease spectrum. In the classification task of NC and MCI, the overall performance of SUVR based on WC_pvc was relatively optimal (AUCs: 0.975-1.000). In the classification task of NC and AD, SUVRs of 10 ROIs based on the WC_pvc method showed the relatively best performance (AUCs: 0.976-1.000). The correlation between SUVR of fusiform based on cerebellar WM and mini-mental state examination (MMSE) score was the strongest ( rs=-0.72, P<0.001), and the SUVR of precuneus based on WC_pvc showed the strongest correlation with clinical dementia rating (CDR) score ( rs=0.78, P<0.001). Conclusion:The SUVR based on WC_pvc method performs well in classification and correlation tasks, and is recommended to be used in semi-quantification of 18F-Florzolotau PET images of AD.

Purpose To investigate the characteristics of 18F-Florbetaben(18F-FBB)β-amyloid(Aβ)PET imaging in different brain regions of Alzheimer's disease(AD)patients with different degrees of cognitive impairment,and to explore the correlation between Aβ deposition and cognitive dysfunction.Materials and Methods A total of eighteen patients with a clinical diagnosis of probable AD from August 2022 to October 2023 were retrospectively included in Huashan Hospital.All patients had Aβ abnormal deposition in the brain as confirmed by 18F-FBB PET imaging.According to the severity of symptoms,they were divided into the AD-induced mild cognitive impairment(MCI)group(8 cases)and the dementia group(10 cases).In addition,12 healthy controls were included.First,the standardized uptake value ratio of abnormal Aβ deposition in the frontal lobe,lateral parietal lobe,lateral temporal lobe,anterior and posterior cingulate gyrus,and compound cortex was semi-quantitatively calculated and compared among the three groups based on the subjects'brain MRI and automated anatomical labeling template.The correlation between the degree of Aβ deposition in the brains of AD patients and cognitive scale scores(mini-mental state examination,Montreal cognitive assessment)was then further analyzed.Results The standardized uptake value ratio values of Aβabnormal deposition in the frontal lobe,lateral temporal lobe,lateral parietal lobe,anterior and posterior cingulate cortex and compound cortex in the AD-induced MCI and dementia groups were significantly higher than those in the healthy controls(t=7.442-9.151,all P＜0.05).However,there was no significant difference in the standardized uptake value ratio values of Aβ abnormal deposition in the above brain regions between the MCI and dementia groups(t=0.312-0.996,all P＞0.05).In addition,there was no significant correlation between the degree of Aβ deposition in the brain and the cognitive scale scores(mini-mental state examination,Montreal cognitive assessment)in the AD-induced MCI and dementia groups(r=-0.049-0.050,all P＞0.05).Conclusion Aβ deposition in the brains of AD-induced MCI and dementia is significantly higher than in the healthy controls.However,Aβ deposition cannot identify AD patients with different degrees of cognitive impairment,reflecting that Aβ deposition has certain limitations in assessing the severity of clinical symptoms of AD.

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 perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

Objective:A voxel-level quantification method based on the tau IQ algorithm and Braak staging, excluding β-amyloid (Aβ) imaging, was developed to achieve specific tau quantification. Methods:This cross-sectional study included 92 subjects (35 males, 57 females; age (62.9±10.4) years) from the Nuclear Medicine/PET Center of Huashan Hospital, Fudan University between November 2018 and July 2020. The cohort comprised 28 cognitively normal (CN) individuals, 20 patients with mild cognitive impairment (MCI), and 44 patients with Alzheimer′s disease (AD). All participants underwent 18F-florzolotau PET imaging, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scoring. A longitudinal tau dataset was constructed based on Braak staging. Voxel-level logistic regression fitting provided a baseline matrix, decomposed via least squares to yield the Tau load coefficient. One-way analysis of variance (with post hoc Tukey) was used to compare Tau load and SUV ratio (SUVR) among groups. ROC curve analysis was used to evaluate classification between CN, MCI and AD. Spearman rank correlation was used to assess the relationships between Tau load, SUVR, and MMSE scores or CDR scores. Results:The Tau load in the CN group was close to 0 and significantly lower than that in the MCI and AD groups ( F=55.03, P<0.001; post hoc tests all P<0.001). Significant differences were also observed in the SUVR across all ROIs ( F values: 36.46-55.38, all P<0.001). Compared to SUVR, Tau load demonstrated greater intergroup differences. In ROC curve analyses between each pair of CN, MCI, and AD groups, Tau load consistently achieved the highest AUC (0.754-1.000). Both Tau load and SUVR for each ROI were negatively correlated with MMSE scores ( rs values: from -0.698 to -0.583, all P<0.05) and positively correlated with CDR scores ( rs values: 0.648-0.783, all P<0.05), with Tau load showing the highest absolute correlation coefficients. Conclusion:Compared to the traditional semi-quantitative SUVR method, the Braak-tau IQ algorithm does not require a specific reference brain region to achieve specific tau quantification.

Due to the availability of 18F-FDG in PET centers, this article aims to advocate and promote the standardization of 18F-FDG PET brain imaging in dementia in order to improve the reliability, repeatability and comparison of the imaging process and results. It is also provided to guide the PET imaging operation standard and to give suggestions on image interpretation.

Sarcopenia is a systemic syndrome characterized by decreased muscle mass and muscle strength and decline of motor function.Sarcopenia affects quality of life and disease prognosis of patients seriously, because of the low awareness rate, low treatment rate and high cardiovascular risk. Patients with uremia undergoing peritoneal dialysis are likely to suffer from sarcopenia due to dietary restriction, loss of protein and high catabolism. This article summarizes the diagnostic methods, risk factors, predictive markers and intervention measures for sarcopenia in peritoneal dialysis patients.

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.