Aim To investigate the effect of theaflavin on oxidized low density lipoprotein(ox-LDL)-induced foam cell formation and oxidative stress in THP-1 macrophages and its mechanism.Methods THP-1 derived macro-phages were pretreated with 50 μmol/L theaflavin and(or)10 μmol/L nuclear factor erythroid 2-related factor 2(NRF2)inhibitor ML385,then 100 mg/L ox-LDL was added to the cells for 24 h to establish the foam cell model.The effect of theaflavin on THP-1 macrophages viability was evaluated by CCK-8 assay and LDH release.The expression of inflamma-tory cytokines interleukin-6(IL-6),interleukin-1 β(IL-1β),tumor necrosis factor-α(TNF-α)were analyzed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot.The release of inflammatory cytokines were detected by enzyme linked immunosorbent assay(ELISA).Intracellular lipid accumulation was detected by Oil red O staining,and lipid absorption was observed by DiL-labeled oxidized low density lipoprotein(DiL-ox-LDL)staining.Re-active oxygen species(ROS)level was detected by DCFH-DA probe.The expression of lipid uptake,cholesterol efflux and oxidative stress-related proteins were detected by Western blot and RT-qPCR.Results Treatment with 100 mg/L ox-LDL significantly decreased cell viability and cholesterol efflux-related protein expressions,increased lipid uptake,ac-cumulation and lipid uptake-related protein expressions,and significantly promoted inflammation and ROS level,as well as the expressions of myeloperoxidase(MPO),NADPH oxidase 2(NOX2)in THP-1 macrophages(all P＜0.05).After pretreatment with theaflavin,cell viability was increased,intracellular lipid uptake,accumulation and lipid uptake-related protein expressions were significantly reduced,cholesterol efflux-related protein expressions were significantly increased,the expression and release of IL-6,IL-1β and TNF-α were significantly decreased,ROS level was significantly decreased,and the expression of MPO and NOX2 were decreased(all P＜0.05).Pretreatment with theaflavin effectively alleviated intracellular oxidative stress by altering the expression of NRF2,heme oxygenase-1(HO-1)and Kelch-like ECH-associated protein 1(KEAP1)in NRF2 signaling pathway,and enhanced the translocation of NRF2 into the nucleus.After pretreat-ment with ML385,the expression levels of NRF2,HO-1,KEAP1 and CD36 were significantly decreased.Conclusion Theaflavin can significantly inhibit ox-LDL-induced foam cell formation,inflammation,and oxidative stress through NRF2/HO-1 signaling pathway in THP-1 macrophages.

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:To predict the short-term postoperative recurrence status of patients with refractory temporal lobe epilepsy (TLE) by analyzing preoperative 18F-FDG PET images and patients′ clinical characteristics based on deep residual neural network (ResNet). Methods:Retrospective analysis was conducted on preoperative 18F-FDG PET images and clinical data of 220 patients with refractory TLE (132 males and 88 females, age 23.0(20.0, 30.2) years)) in the First Affiliated Hospital of Jinan University between January 2014 and June 2020. ResNet was used to perform high-throughput feature extraction on preprocessed PET images and clinical features, and to perform a postoperative recurrence prediction task for differentiating patients with TLE. The predictive performance of ResNet model was evaluated by ROC curve analysis, and the AUC was compared with that of classical Cox proportional risk model using Delong test. Results:Based on PET images combined with clinical feature training, AUCs of the ResNet in predicting 12-, 24-, and 36-month postoperative recurrence were 0.895±0.073, 0.861±0.058 and 0.754±0.111, respectively, which were 0.717±0.093, 0.697±0.081 and 0.645±0.087 for Cox proportional hazards model respectively ( z values: -3.00, -2.98, -1.09, P values: 0.011, 0.018, 0.310). The ResNet showed best predictive effect for recurrence events within 12 months after surgery. Conclusion:The ResNet model is expected to be used in clinical practice for postoperative follow-up of patients with TLE, helping for risk stratification and individualized management of postoperative patients.

tRNA-derived small RNAs (tsRNAs) are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases. However, their exact presence and function in hepatocellular carcinoma (HCC) remain unclear. Here, differentially expressed tsRNAs in HCC were profiled. A novel tsRNA, tRNA^Gln-TTG derived 5'-tiRNA-Gln, is significantly downregulated, and its expression level is correlated with progression in patients. In HCC cells, 5'-tiRNA-Gln overexpression impaired the proliferation, migration, and invasion in vitro and in vivo, while 5'-tiRNA-Gln knockdown yielded opposite results. 5'-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I (EIF4A1), which unwinds complex RNA secondary structures during translation initiation, causing the partial inhibition of translation. The suppressed downregulated proteins include ARAF, MEK1/2 and STAT3, causing the impaired signaling pathway related to HCC progression. Furthermore, based on the construction of a mutant 5'-tiRNA-Gln, the sequence of forming intramolecular G-quadruplex structure is crucial for 5'-tiRNA-Gln to strongly bind EIF4A1 and repress translation. Clinically, 5'-tiRNA-Gln expression level is negatively correlated with ARAF, MEK1/2, and STAT3 in HCC tissues. Collectively, these findings reveal that 5'-tiRJNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Eukaryotic Initiation Factor-4A/genetics* ; Cell Line ; RNA, Transfer/metabolism* ; RNA ; Cell Proliferation

OBJECTIVES: To develop a Chinese version of the Stress Adaption Scale (SAS) and to assess its reliability and validity among Chinese patients with multimorbidity. METHODS: The Brislin model was used to translate, synthesize, back-translate, and cross culturally adapt the SAS. A total of 323 multimorbidity patients selected by convenience sampling method from four hospitals in Zhejiang province. The critical ratio method, total question correlation method, and graded response model (item characteristic curve and item discrimination) were used for item analysis. Cronbach's alpha coefficient and split-half reliability were used for the reliability analysis. Content validity analysis, structural validity analysis, and criterion association validity analysis were performed by expert scoring method, confirmatory factor analysis, and Pearson correlation coefficient method, respectively. RESULTS: The Chinese version of the SAS contained 2 dimensions of resilience and thriving, with a total of 10 items. In the item analysis, the critical ratio method showed that the critical ratio of all items was greater than 3.0 (P<0.001); the correlation coefficient method showed that the Pearson correlation coefficients for all items exceeded 0.4 (P<0.01). The graded response model showed that items of the revised scale exhibited distinct item characteristic curves and all items had discrimination parameters exceeding 1.0. In the reliability analysis, Cronbach's alpha coefficient of the revised Chinese version of the SAS scale was 0.849, and the split-half reliability was 0.873. In the validity analysis, the item-level content validity index and scale-level content validity index both exceeded 0.80. In the confirmatory factor analysis, the revised two-factor model showed satisfactory fit indices (χ²/df=3.115, RMSEA=0.081, RMR=0.046, GFI=0.937, AGFI=0.898, CFI=0.936, TLI=0.915). In the criterion-related validity analysis, the Chinese version of the SAS score was negatively correlated with the Perceived Stress Scale and the Treatment Burden Questionnaire, with correlation coefficients of －0.592 and －0.482, respectively (both P<0.01). CONCLUSIONS The Chinese version of the SAS has good reliability and validity, which can be used to evaluate the stress adaption capacity among multimorbidity patients in China, and provides a reference for developing individualized health management measures.
Humans ; Adaptation, Psychological ; Asian People ; China ; Multimorbidity ; Reproducibility of Results ; Stress, Psychological/psychology* ; Surveys and Questionnaires ; Translating ; Cross-Cultural Comparison

OBJECTIVES: To develop a Chinese version of the Long-Term Conditions Questionnaire (LTCQ) and to test its reliability and validity in Chinese patients with chronic diseases. METHODS: With the consent of the original authors, a Chinese version of LTCQ was developed according to the cultural adjustment guidelines. A questionnaire survey was conducted on 319 patients with chronic diseases in Sir Run Run Shaw Hospital, Wuyi County First People's Hospital and Hangzhou Gongchen Bridge Street Health Service Center. The questionnaire was evaluated by item analysis (including frequency analysis, total question correlation method and critical ratio method), reliability analysis (Cronbach's alpha coefficient) and validity analysis [including content validity (expert scoring method) and structural validity (exploratory factor analysis)]. RESULTS The Chinese version of the LTCQ included 20 entries, with a Cronbach's alpha coefficient of 0.926, a retest reliability of 0.829, a split-half reliability of 0.878, an entry content validity index of 1, and a content validity index at the questionnaire level of 1. Four common factors were extracted by exploratory factor analysis, namely physical state and daily life, psychological state, support and coping, and safe environment, with a cumulative variance contribution rate of 67.244%. Discussion: The Chinese version of the LTCQ developed in this study has good reliability and validity and it may be used to assess the long-term conditions of patients with chronic diseases in China.
Humans ; Asian People ; China ; Chronic Disease ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

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 potential application of combining 18F-FDG PET imaging and radiomics in the diagnosis of Parkinson′s disease (PD) and atypical parkinsonian syndromes (APS). Methods:A total of 154 subjects of two cohorts (training set and validation set) were enrolled from Huashan Hospital, Fudan University from March 2015 to August 2020 in this cross-sectional study, including 40 normal controls (NC; 23 males and 17 females, age: (60.2±10.5) years), 40 PD patients (20 males and 20 females, age: (64.7±6.3) years), 40 progressive supranuclear palsy (PSP) patients (20 males and 20 females, age: (64.1±5.9) years), and 34 multiple system atrophy (MSA) patients (19 males and 15 females, age: (65.0±9.2) years). 18F-FDG PET images and clinical scale were selected, and one-way analysis of variance was used to compare differences of clinical scale among groups. Radiomic features extraction and feature selection were carried out. Two and three classification models were constructed based on logistic regression, and the ROC curves of clinical model, radiomics model and combined model were calculated. Independent classification tests were conducted 100 times with 5-fold cross validation in two cohorts. Results:There were significant differences in the scores of unified PD Rating Scale (UPDRS) and Hoehn-Yahr rating scale (H&Y) among different groups in cohort 1 and cohort 2 respectively ( F values: 4.83-17.95, all P<0.05). A total of 2 444 imaging features were extracted from each subject, and after features selection, 15 features for classification were obtained. In the two classification experiment, the AUCs of the three models in binary classification of PD/MSA/PSP/NC group were 0.56-0.68, 0.74-0.93 and 0.72-0.93, respectively. The classification effects of the radiomics model were significantly better than those of the clinical model ( z values: 1.71-2.85, all P<0.05). In the three classification experiment, the sensitivity of the radiomics model reached 80%, 80% and 77% for PD, MSA and PSP, respectively. Conclusion:18F-FDG imaging combined with radiomics has potential in the diagnosis of PD and APS.