The Effect of Bullying Victimization on Adolescent Non-Suicidal Self-Injury: The Mediating Roles of Alexithymia and Self-Esteem.

Background & Aim: Non-suicidal self-injury (NSSI) in adolescents is a serious public health issue influenced by the interaction of multiple factors. The purpose of this study was to investigate the multiple mediating roles of alexithymia and self-esteem in the association between bullying victimization and NSSI in a sample of Chinese adolescents. Methods: A survey of 1299 adolescents from two public middle schools in Henan Province, China, was undertaken. Data were collected using the Chinese version of the Delaware bullying victimization scale-student (DBVS-S), the Toronto Alexithymia-20 Scale (TAS-20-C), the Rosenberg self-esteem scale (RSES), and the adolescent self-injury questionnaire. Besides, we performed a structural equation modeling (SEM) with latent variables using AMOS 26.0 to examine the relationship between variables and the mediating effects. Results: The SEM analysis found that not only can bullying victimization directly impact NSSI, but that alexithymia and self-esteem have a chain mediating effect in the association between bullying victimization and NSSI. This mediating effect contributed 22.47% to the total effect. Conclusion: These findings validate bullying victimization, alexithymia, and low self-esteem are important variables that affect NSSI among Chinese adolescents. Educators need to implement some prevention and intervention strategies to ameliorate the campus atmosphere and adolescents' mental health aimed at avoiding NSSI behavior in adolescence.

MbovP0725, a secreted serine/threonine phosphatase, inhibits the host inflammatory response and affects metabolism in Mycoplasma bovis.

Mycoplasma species are able to produce and release secreted proteins, such as toxins, adhesins, and virulence-related enzymes, involved in bacteria adhesion, invasion, and immune evasion between the pathogen and host. Here, we investigated a novel secreted protein, MbovP0725, from Mycoplasma bovis encoding a putative haloacid dehalogenase (HAD) hydrolase function of a key serine/threonine phosphatase depending on Mg2+ for the dephosphorylation of its substrate pNPP, and it was most active at pH 8 to 9 and temperatures around 40°C. A transposon insertion mutant strain of M. bovis HB0801 that lacked the protein MbovP0725 induced a stronger inflammatory response but with a partial reduction of adhesion ability. Using transcriptome sequencing and quantitative reverse transcription polymerase chain reaction analysis, we found that the mutant was upregulated by the mRNA expression of genes from the glycolysis pathway, while downregulated by the genes enriched in ABC transporters and acetate kinase-phosphate acetyltransferase pathway. Untargeted metabolomics showed that the disruption of the Mbov_0725 gene caused the accumulation of 9-hydroxyoctadecadienoic acids and the consumption of cytidine 5'-monophosphate, uridine monophosphate, and adenosine monophosphate. Both the exogenous and endogenous MbvoP0725 protein created by purification and transfection inhibited lipopolysaccharide (LPS)-induced IL-1ß, IL-6, and TNF-α mRNA production and could also attenuate the activation of MAPK-associated pathways after LPS treatment. A pull-down assay identified MAPK p38 and ERK as potential substrates for MbovP0725. These findings define metabolism- and virulence-related roles for a HAD family phosphatase and reveal its ability to inhibit the host pro-inflammatory response. IMPORTANCE: Mycoplasma bovis (M. bovis) infection is characterized by chronic pneumonia, otitis, arthritis, and mastitis, among others, and tends to involve the suppression of the immune response via multiple strategies to avoid host cell immune clearance. This study found that MbovP0725, a haloacid dehalogenase (HAD) family phosphatase secreted by M. bovis, had the ability to inhibit the host pro-inflammatory response induced by lipopolysaccharide. Transcriptomic and metabolomic analyses were used to identify MbovP0725 as an important phosphatase involved in glycolysis and nucleotide metabolism. The M. bovis transposon mutant strain T8.66 lacking MbovP0725 induced a higher inflammatory response and exhibited weaker adhesion to host cells. Additionally, T8.66 attenuated the phosphorylation of MAPK P38 and ERK and interacted with the two targets. These results suggested that MbovP0725 had the virulence- and metabolism-related role of a HAD family phosphatase, performing an anti-inflammatory response during M. bovis infection.

Filamentous prophage Pf4 promotes genetic exchange in Pseudomonas aeruginosa.

Filamentous prophages are widespread among bacteria and play crucial functions in virulence, antibiotic resistance, and biofilm structures. The filamentous Pf4 particles, extruded by an important pathogen Pseudomonas aeruginosa, can protect producing cells from adverse conditions. Contrary to the conventional belief that the Pf4-encoding cells resist reinfection, we herein report that the Pf4 prophage is reciprocally and commonly exchanged within P. aeruginosa colonies, which can repair defective Pf4 within the community. By labeling the Pf4 locus with antibiotic resistance and fluorescence markers, we demonstrate that the Pf4 locus is frequently exchanged within colony biofilms, in artificial sputum media, and in infected mouse lungs. We further show that Pf4 trafficking is a rapid process and capable of rescuing Pf4-defective mutants. The Pf4 phage is highly adaptable and can package additional DNA doubling its genome size. We also report that two clinical P. aeruginosa isolates are susceptible to the Pf4-mediated exchange, and the Pf5 prophage can be exchanged between cells as well. These findings suggest that the genetic exchanging interactions by filamentous prophages may facilitate defect rescue and the sharing of prophage-dependent benefits and costs within the P. aeruginosa community.

Evaluation of lymphotoxin-alpha in pterygium and diagnostic value in active and inactive pterygium states.

To explore the correlation between tear LT-a, pterygium status, and dry eye indicators. We established a diagnostic model to evaluate active pterygium. A retrospective study was conducted between June 2021 and June 2023 on 172 patients, comprising 108 men and 64 women. The study analyzed LT-a and various ocular parameters in all participants. The data was collected using Excel software and analyzed using SPSS 25.0 statistical software and Medcalc. We made a nomogram diagnostic model to different diagnosed the state of pterygium. This study found that pterygium has progressive eye surface damage during the active state. There was no significant difference in dry eye indicators between the two groups. However, the concentration of LT-a in the active group was significantly lower than that in the inactive group (P < 0.001). We observed that increased pterygium grade corresponded to a worse ocular surface condition. In addition, LT-a was significantly positively correlated with disease duration, but negatively correlated with age, pterygium size, active pterygium state, and LLT value. The optimal intercept value for evaluating active pterygium in Lt-a was ≤ 0.49 dg/ml. We screened three variables for evaluating active pterygium through Single and Multiple regression analysis: LT-a grading, pterygium size, and congestion score. Finally, we made a reliable diagnostic nomogram model. Pterygium development triggers immune inflammation. Our model based on LT-a identifies active pterygium for personalized treatment options and new research directions.

Dynamic total-body PET/CT imaging with reduced acquisition time shows acceptable performance in quantification of [18F]FDG tumor kinetic metrics.

PURPOSE: To investigate the feasibility of reducing the acquisition time for continuous dynamic positron emission tomography (PET) while retaining acceptable performance in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in tumors. METHODS: In total, 78 oncological patients underwent total-body dynamic PET imaging for ≥ 60 min, with 8, 20, and 50 patients receiving full activity (3.7 MBq/kg), half activity (1.85 MBq/kg), and ultra-low activity (0.37 MBq/kg) of [18F]FDG, respectively. The dynamic data were divided into 21-, 30-, 45- and ≥ 60-min groups. The kinetic analysis involved model fitting to derive constant rates (VB, K1 to k3, and Ki) for both tumors and normal tissues, using both reversible and irreversible two-tissue-compartment models. One-way ANOVA with repeated measures or the Freidman test compared the kinetic metrics among groups, while the Deming regression assessed the correlation of kinetic metrics among groups. RESULTS: All kinetic metrics in the 30-min and 45-min groups were statistically comparable to those in the ≥ 60-min group. The relative differences between the 30-min and ≥ 60-min groups ranged from 12.3% ± 15.1% for K1 to 29.8% ± 30.0% for VB, and those between the 45-min and ≥ 60-min groups ranged from 7.5% ± 8.7% for Ki to 24.0% ± 24.3% for VB. However, this comparability was not observed between the 21-min and ≥ 60-min groups. The significance trend of these comparisons remained consistent across different models (reversible or irreversible), administrated activity levels, and partial volume corrections for lesions. Significant correlations in tumor kinetic metrics were identified between the 30-/45-min and ≥ 60-min groups, with Deming regression slopes > 0.813. In addition, the comparability of kinetic metrics between the 30-min and ≥ 60-min groups were established for normal tissues. CONCLUSION: The acquisition time for dynamic PET imaging can be reduced to 30 min without compromising the ability to reveal tumor kinetic metrics of [18F]FDG, using the total-body PET/CT system.

One-tenth-activity total-body positron emission tomography versus full-activity imaging in patients with a complex of hepatic malignant tumors: a retrospective study.

Background: The value of ultra-low-activity 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging in patients with hepatic malignancies remains unclear. Methods: A cross-sectional study was conducted from April 2019 to May 2021 in Zhongshan Hospital, Fudan University. A total of 49 patients with hepatic malignancies, including hepatocellular carcinoma (HCC) (n=13) or intrahepatic cholangiocarcinoma (ICC) (n=36), underwent 60-min dynamic PET imaging, with 15 undergoing full-activity 18F-FDG and 34 undergoing ultra-low-activity 18F-FDG. The kinetic metrics (K1-k3, and Ki) of tumors were calculated and compared between the activity groups. Another 54 patients (27 each group) with hepatic malignancies, including HCC (n=9), ICC (n=34), and metastases (n=11), underwent static imaging. Image qualities were compared between the groups in terms of 5-point Likert scores (with a score ≥3 fulfilling the clinical requirement), the mean standardized uptake value (SUVmean), the standard deviation of standardized uptake value (SUVSD), and the signal-to-noise ratio (SNR) of the liver; the SUVmean of blood pool and muscle; and the tumor-to-liver ratio (TLR), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of lesions. Intergroup comparisons were performed using Chi-squared test for categorical variables and the Student's t-test or the Mann-Whitney test for continuous variables depending on the normality of variables. Results: There was a nonsignificant difference in the kinetic metrics (K1-k3 and Ki) of tumors between the activity groups. In static imaging, 1-min full-activity (F1) and 8-min ultra-low-activity (L8) images obtained image-quality scores >3 and were thus selected for intergroup comparisons. Nonsignificant differences in SUVmean of liver, blood pool, and muscle were identified between F1 and L8 images (P=0.641, P=0.542, and P=0.073, respectively) although the liver SNR was slightly higher in F1 (13.10 vs. 11.31; P=0.003). Lesion detectability was 98.5% and 100% for F1 and L8 images, respectively, but there were no significant differences in TLR, TBR, or TMR between the groups. Conclusions: The results of this single-center study indicate that the performance of ultra-low-activity PET imaging is comparable to that of full-activity imaging in patients with hepatic malignancies.

Different hydration protocols for the quantification of healthy tissue uptake of half-dose 18F-FDG total-body positron emission tomography-computed tomography: a prospective study.

Background: This study aimed to investigate the effects of the volume and time of hydration on the quantification of healthy tissue uptake for 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) total-body positron emission tomography (PET)-computed tomography (CT) with half-dose activity. Methods: This study prospectively enrolled 180 patients who underwent a total-body PET-CT scan 10 min after injection of a half-dose (1.85 MBq/kg) of 18F-FDG. These patients were placed in hydration groups (30 patients in each group) according to different hydration volumes and times: oral hydration with 500 mL of water 20 min before (G1), 5 min after (G2), and 30 min after (G3) the 18F-FDG injection; and oral hydration with 200 mL of water 20 min before (G4), 5 min after (G5), and 30 min after (G6) the 18F-FDG injection. Another 30 patients underwent dynamic imaging without hydration and were used a nonhydration group. The analysis of quantification of healthy tissue uptake included the maximum standardized uptake value (SUVmax) and the mean SUV (SUVmean) of the blood pool and muscle, as well as the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver. Results: The SUVmax of the blood pool (2.33±0.36), liver (3.03±0.42), and muscle (0.81±0.15) was significantly higher in the nonhydration group than in any of the 6 hydrated groups (P<0.05 for all hydration groups vs. nonhydration group). Muscle SUVmax and SUVmean were significantly (P<0.05) lower in G1 and G2 than in G3 and were lower in G4 and G5 than in G6. The SUVmax and SUVmean of the blood pool were significantly (P<0.05) lower in G1 than in G3 and G4 and lower in G3 than in G6. Conclusions: When total-body PET-CT with a half dose of 18F-FDG activity is performed, hydration can significantly affect the quantification of healthy tissue uptake. Oral administration of 500 mL of water 20 min before injection could reduce background radioactivity.

Combined early dynamic 18F-FDG PET/CT and conventional whole-body 18F-FDG PET/CT in hepatocellular carcinoma.

OBJECTIVE: To investigate the diagnostic value of early dynamic 18F-FDG PET/CT(ED 18F-FDG PET/CT) combined with conventional whole-body 18F-FDG PET/CT(WB 18F-FDG PET/CT) in hepatocellular carcinoma (HCC), as well as the difference of early dynamic blood flow parameters and maximum standardized uptake value (SUVmax) in HCC patients with/without liver cirrhosis or microvascular invasion (MVI). METHODS: Twenty-two consecutive patients (mean age 57.8 years) with 28 established HCC lesions (mean size 4.5 cm) underwent a blood flow study with an 18F-FDG dynamic scan divided into 24 sequences of 5 s each and a standard PET/CT scan. On the ED PET/CT study, an experienced PET/CT physician obtained volumes of interest (VOIs) where three blood flow estimates (time to peak [TTP], blood flow [BF], and hepatic perfusion index [HPI]) were calculated. On the WB PET/CT study, a VOI was placed on the fused scan for each HCC and maximum standardized uptake value (SUVmax) was obtained. Comparison of blood flow estimates, SUVmax, and tumor/background ratio (TNR) was performed among HCCs with and without angioinvasion, as well as HCCs in cirrhotic and non-cirrhotic liver. RESULTS: Compared with WB 18F-FDG PET/CT alone, ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs (both P < 0.05). HPI was higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis (P = 0.044). There was no significant difference in TTP, BF, SUVmax, or TNR between HCCs in patients with liver cirrhosis and those without liver cirrhosis. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without cirrhosis. TTP was shorter in HCCs with MVI than without MVI (P = 0.046). There was no significant difference in BF, HPI, SUVmax, or TNR between HCCs with MVI and without MVI. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without MVI. CONCLUSION: ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs. HPI was significantly higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis. TTP was significantly shorter in HCCs with MVI than without MVI.

Comparison of 18F-FDG PET/MR and PET/CT for pretreatment TNM staging of hilar cholangiocarcinoma.

PURPOSE: 18F-FDG PET/MR has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MR in hilar cholangiocarcinoma (HCCA) are rare. We investigated the value of PET/MR for preoperative staging and compared it with PET/CT in HCCA. METHODS: Fifty-eight patients with HCCA confirmed by pathology were retrospectively analyzed. 18F-FDG PET/CT imaging was performed first, followed with whole-body PET/MR imaging. SUVmax of tumor and normal liver tissue were measured. Paired T test was used to compare SUVmax of tumor and normal liver tissue of PET/CT and PET/MR. In addition, McNemar test was used to compare the accuracy of TNM staging and Bismuth-Corlette typing between PET/CT and PET/MR. RESULTS: There was no significant difference in SUVmax between PET/CT and PET/MR in primary tumor lesions (6.6 ± 5.5 vs. 6.8 ± 6.2, P = 0.439). SUVmax of PET/CT and PET/MR in normal liver parenchyma was significantly different (3.0 ± 0.5 vs. 2.1 ± 0.5, P < 0.001). The accuracy of PET/MR in diagnosing T staging and N staging was significantly higher than those of PET/CT (72.4% vs. 58.6%, P = 0.022 and 84.5% vs. 67.2%, P = 0.002). There was no significant difference between PET/CT and PET/MR in M staging (94.8% vs. 98.3%, P = 0.5). The classification accuracy of PET/MR in Bismuth-Corlette was significantly higher than that of PET/CT (89.7% vs. 79.3%), P = 0.031. CONCLUSIONS: The diagnostic accuracy of 18F-FDG PET/MR was superior to that of PET/CT in preoperative T staging, N staging, and Bismuth-Corlette classification of HCCA. In M staging, the diagnostic accuracy of PET/MR was similar to that of PET/CT.

Caged Luciferase Inhibitor-Based Bioluminescence Switching Strategy Enables Efficient Detection of Serum APN Activity and the Identification of Its Roles in Metastasis of Non-Small Cell Lung Cancer.

Bioluminogenic probes emerged as powerful tools for imaging and analysis of various bioanalyses, but traditional approaches would be limited to the low sensitivity during determine the low activity of protease in clinical specimens. Herein, we proposed a caged luciferase inhibitor-based bioluminescence-switching strategy (CLIBS) by using a cleavable luciferase inhibitor to modulate the activity of luciferase reporter to amplify the detective signals, which led to the enhancement of detection sensitivity, and enabled the determination of circulating Aminopeptidase N (APN) activity in thousands of times diluted serum. By applying the CLIBS to serum samples in non-small cell lung cancer (NSCLC) patients from two clinical cohorts, we revealed that, for the first time, higher circulating APN activities but not its concentration, were associated with more NSCLC metastasis or higher metastasis stages by subsequent clinical analysis, and can serve as an independent factor for forecasting NSCLC patients' risk of metastasis.

Efficacy and safety of ablative CO2 fractional laser and narrowband intense pulsed light for the treatment of hypertrophic scars: a prospective, randomized controlled trial.

BACKGROUND AND OBJECTIVES: Hypertrophic scarring is a complex process, and numerous methods have been introduced to treat scars. This study aims to evaluate the effect of combined CO2 fractional laser and narrowband intense pulsed light (IPL) compared to IPL alone in the treatment of hypertrophic scars. MATERIALS AND METHODS: This was a prospective, randomized controlled study enrolled 138 patients with hypertrophic scars. The participants were randomly divided into two groups: CO2-IPL and IPL group, and received three sessions at 10-14-week intervals for 3-month follow-up. Two independent plastic surgeons evaluated the treatments using the Patient and Observer Scar Assessment Scales (POSAS). Overall satisfaction was evaluated using the Patient Satisfaction Scale (PSS). RESULTS: 101 subjects completed the study. Compared to single IPL, the combination CO2-IPL group showed a significant improvement in itching, color, stiffness, thickness, and irregularity, except for pain, and an enhancement in vascularization, pigmentation, thickness, relief, and pliability of the scar, assessed by POSAS (p < .01). 100% patients in the combination group were satisfied compared to 84% in IPL alone. CONCLUSION: The combination of CO2 fractional laser and narrowband IPL efficiently improved the appearance and profile of hypertrophic scars, offering a comprehensive and reliable approach for scar therapy.

An exploration of the feasibility and clinical value of half-dose 5-h total-body 18F-FDG PET/CT scan in patients with Takayasu arteritis.

PURPOSE: To explore the feasibility and clinical value of 5-h delayed 18F-fluorodeoxyglucose (18F-FDG) total-body (TB) positron emission tomography/computed tomography (PET/CT) in patients with Takayasu arteritis (TA). METHODS: This study included nine healthy volunteers who underwent 1-, 2.5-, and 5-h triple-time TB PET/CT scans and 55 patients with TA who underwent 2- and 5-h dual-time TB PET/CT scans with 1.85 MBq/kg 18F-FDG. The liver, blood pool, and gluteus maximus muscle signal-to-noise ratios (SNRs) were calculated by dividing the SUVmean by its standard deviation to evaluate imaging quality. TA lesions' 18F-FDG uptake was graded on a three-point scale (I, II, III), with grades II and III considered positive lesions. Lesion-to-blood maximum standardised uptake value (SUVmax) ratio (LBR) was calculated by dividing the lesion SUVmax by the blood pool SUVmax. RESULTS: The liver, blood pool, and muscle SNR of the healthy volunteers at 2.5- and 5-h were similar (0.117 and 0.115, respectively, p = 0.095). We detected 415 TA lesions in 39 patients with active TA. The average 2- and 5-h scan LBRs were 3.67 and 7.59, respectively (p < 0.001). Similar TA lesion detection rates were noted in the 2-h (92.0%; 382/415) and 5-h (94.2%; 391/415) scans (p = 0.140). We detected 143 TA lesions in 19 patients with inactive TA. The 2- and 5-h scan LBRs were 2.99 and 5.71, respectively (p < 0.001). Similar positive detection rates in inactive TA were noted in the 2-h (97.9%; 140/143) and 5-h (98.6%; 141/143) scans (p = 0.500). CONCLUSION: The 2- and 5-h 18F-FDG TB PET/CT scans had similar positive detection rates, but both combined could better detect inflammatory lesions in patients with TA.

VgrG Spike Dictates PAAR Requirement for the Assembly of the Type VI Secretion System.

Widely employed by Gram-negative pathogens for competition and pathogenesis, the type six protein secretion system (T6SS) can inject toxic effectors into neighboring cells through the penetration of a spear-like structure comprising a long Hcp tube and a VgrG-PAAR spike complex. The cone-shaped PAAR is believed to sharpen the T6SS spear for penetration but it remains unclear why PAAR is required for T6SS functions in some bacteria but dispensable in others. Here, we report the conditional requirement of PAAR for T6SS functions in Aeromonas dhakensis, an emerging human pathogen that may cause severe bacteremia. By deleting the two PAAR paralogs, we show that PAAR is not required for T6SS secretion, bacterial killing, or specific effector delivery in A. dhakensis. By constructing combinatorial PAAR and vgrG deletions, we demonstrate that deletion of individual PAAR moderately reduced T6SS functions but double or triple deletions of PAAR in the vgrG deletion mutants severely impaired T6SS functions. Notably, the auxiliary-cluster-encoded PAAR2 and VgrG3 are less critical than the main-cluster-encoded PAAR1 and VgrG1&2 proteins to T6SS functions. In addition, PAAR1 but not PAAR2 contributes to antieukaryotic virulence in amoeba. Our data suggest that, for a multi-PAAR T6SS, the variable role of PAAR paralogs correlates with the VgrG-spike composition that collectively dictates T6SS assembly. IMPORTANCE Gram-negative bacteria often encode multiple paralogs of the cone-shaped PAAR that sits atop the VgrG-spike and is thought to sharpen the spear-like T6SS puncturing device. However, it is unclear why PAAR is required for the assembly of some but not all T6SSs and why there are multiple PAARs if they are not required. Our data delineate a VgrG-mediated conditional requirement for PAAR and suggest a core-auxiliary relationship among different PAAR-VgrG modules that may have been acquired sequentially by the T6SS during evolution.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

An artificial intelligence-driven image quality assessment system for whole-body [18F]FDG PET/CT.

PURPOSE: Image quality control is a prerequisite for applying PET/CT. This study aimed to develop an artificial intelligence-driven real-time and accurate whole-body [18F]FDG PET/CT image quality assessment system. METHODS: This study included 173 patients (age, 59 ± 12 years; 66.3% males) with whole-body [18F]FDG PET/CT imaging. Images of ten patients were used as an educational set. Images of the rest 163 patients were reconstructed to 952 images by simulating several scanning times and randomly split into training (60%, 98 patients, 578 images), validation (20%, 33 patients, 192 images), and test (20%, 32 patients,182 images) sets. Two experienced physicians (R1 and R2) independently assessed the image quality of thorax, abdomen, and pelvis region twice (R1a and b; R2a and b), 1 month apart, using a 5-point Likert scale. Objective image quality metrics were extracted from the mediastinal blood pool, three liver levels, and the bilateral gluteus maximus. The developed convolutional neural networks for image quality assessment (IQA-CNNs) generated the subjective quality scores and objective image metrics. The IQA-CNNs and physicians' performances were compared for localization accuracy, score agreement, and process time. RESULTS: The physicians demonstrated good inter- and intra-rater subjective assessment agreement, with kappa coefficients (R1a vs. R2a, R1a vs. R1b, R2a vs. R2b, and R1a vs. R2b) of 0.78, 0.77, 0.76, and 0.80. The IQA-CNNs and R1 or R2 agreed in the subjective assessments, with kappa coefficients of 0.79 and 0.78. IQA-CNNs and R1 or R2 also agreed in their objective image quality assessment (ICC > 0.60). The IQA-CNNs evaluation speed was 200 times faster than the manual assessment. CONCLUSION: An automated system for rapid assessment of [18F]FDG PET/CT image quality was developed, showing comparable performance to senior physicians. The system generates a comprehensive and detailed image quality assessment report, including subjective visual scores and objective image metrics for various anatomical regions.

A personal acquisition time regimen of 68Ga-DOTATATE total-body PET/CT in patients with neuroendocrine tumor (NET): a feasibility study.

BACKGROUND: The injection activity of tracer, acquisition time, patient-specific photon attenuation, and large body mass, can influence on image quality. Fixed acquisition time and body mass related injection activity in clinical practice results in a large difference in image quality. Thus, this study proposes a patient-specific acquisition time regimen of 68 Ga-DOTATATE total-body positron emission tomography-computed tomography (PET/CT) to counteract the influence of body mass (BM, kg) on image quality, and acquire an acceptable and constant image of patients with neuroendocrine tumors (NETs). METHODS: The development cohort consisting of 19 consecutive patients with full activity (88.7-204.9 MBq, 2.0 ± 0.1 MBq/kg) was to establish the acquisition time regimen. The liver SNR (signal-to-noise ratio, SNRL) was normalized (SNRnorm) by the product of injected activity (MBq) and acquisition time (min). Fitting of SNRnorm against body mass (BM, kg) in linear correlation was performed. Subjective assessment of image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL, and an optimized acquisition regimen based on BM was proposed, and validated its feasibility through the validation cohort of 57 consecutive NET patients with half activity (66.9 ± 11.3 MBq, 1.0 ± 0.1 MBq/kg) and a fixed acquisition time regimen. RESULTS: The linear correlation (R2 = 0.63) between SNRnorm and BM (kg) was SNRnorm = -0.01*BM + 1.50. The threshold SNRL of acceptable image quality was 11.2. The patient-specific variable acquisition time regimen was determined as: t (min) = 125.4/(injective activity)*(-0.01*BM + 1.50)2. Based on that proposed regimen, the average acquisition time for acceptable image quality in the validation cohort was 2.99 ± 0.91 min, ranging from 2.18 to 6.35 min, which was reduced by 36.50% ~ 78.20% compared with the fixed acquisition time of 10 min. Subjective evaluation showed that acceptable image quality could be obtained at 3.00 min in the validation group, with an average subjective score of 3.44 ± 0.53 (kappa = 0.97, 95% CI: 0.96 ~ 0.98). Bland-Altman analysis revealed good agreement between the proposed regimen and the fixed acquisition time cohort. CONCLUSION: A patient-specific acquisition time regimen was proposed in NET patients in development cohort and validated its feasibility in patients with NETs in validation cohort by 68 Ga-DOTATATE total-body PET/CT imaging. Based on the proposed regimen, the homogenous image quality with optimal acquisition time was available independent of body mass.

HSP70 alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial dysfunction-initiated NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes.

Background: Sepsis-induced cardiomyopathy (SIC) is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality. Heat shock proteins (HSPs) have been implicated in suppressing septic inflammation. The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction, exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention. Methods: Mice with cecal ligation plus perforation (CLP) and lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes were used as models of SIC. The mouse survival rate, gross profile, cardiac function, pathological changes and mitochondrial function were observed by photography, echocardiography, hematoxylin-eosin staining and transmission electron microscopy. In addition, cell proliferation and the levels of cardiac troponin I (cTnI), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by Cell Counting Kit-8, crystal violet staining and enzyme-linked immunosorbent assay. Moreover, mitochondrial membrane potential was assessed by immunofluorescence staining, and dynamin-related protein 1 and pyroptosis-related molecules [nucleotide-binding domain, leucine-rich-repeat containing family pyrin domain-containing 3 (NLRP3), caspase-1, gasdermin-D (GSDMD), gasdermin-D N-terminal (GSDMD-N)] were measured by western blotting, immunoprecipitation and immunoblotting. Finally, hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism. Results: Models of SIC were successfully established, as reduced consciousness and activity with liparotrichia in CLP mice were observed, and the survival rate and cardiac ejection fraction (EF) were decreased; conversely, the levels of cTnI, TNF-α and IL-1ß and myocardial tissue damage were increased in CLP mice. In addition, LPS stimulation resulted in a reduction in cell viability, mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro. HSP70 treatment improved myocardial tissue damage, survival rate and cardiac dysfunction caused by CLP. Additionally, HSP70 intervention reversed LPS-induced mitochondrial destabilization, inhibited activation of the NLRP3 inflammasome, caspase-1, GSDMD and GSDMD-N, and decreased pyroptosis. Finally, knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity, and exogenous HSP70 significantly rescued these changes. It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules. Conclusions: Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC. Interestingly, HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the activation of NLRP3 inflammasome-mediated pyroptosis, and such a result may provide approaches for novel therapies for SIC.

Annexin A2 regulates Mycoplasma bovis adhesion and invasion to embryo bovine lung cells affecting molecular expression essential to inflammatory response.

Mycoplasma bovis (M. bovis) is an important pathogen of the bovine respiratory disease complex, invading lower respiratory tracts and causing severe pneumonia. However, its molecular mechanism largely remains unknown. Host annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein. The current study sought to determine whether ANXA2 could mediate M. bovis adhesion and invasion thereby affecting its induction of inflammatory response. ANXA2 expression was upregulated in M. bovis-infected bovine lung epithelial cells (EBL), and blocking ANXA2 with an anti-ANXA2 antibody reduced M. bovis adhesion to EBL. Compared with uninfected cells, more ANXA2 was translocated from the cytoplasm to the cell surface after M. bovis infection. Furthermore, RNA interference knockdown of ANXA2 expression in EBL cells resulted in a significant decrease in M. bovis invasion and F-actin polymerization. Next, the transcriptomic study of M. bovis-infected EBL cells with and without ANXA2 knockdown were performed. The data exhibited that ANXA2 knockdown EBL cells had 2487 differentially expressed genes (DEGs), with 1175 upregulated and 1312 downregulated compared to control. According to GO and KEGG analyses, 50 genes potentially linked to inflammatory responses, 23 involved in extracellular matrix (ECM) receptor interaction, and 48 associated with PI3K-AKT signal pathways were upregulated, while 38 mRNA binding genes, 16 mRNA 3'-UTR binding genes, and 34 RNA transport genes were downregulated. Furthermore, 19 genes with various change-folds were selected for qPCR verification, and the results agreed with the RNA-seq findings. Above all, the transcription of two chemokines (IL-8 and CXCL5) and a key bovine ß-defensin TAP in IL-17 signaling pathway were significantly increased in ANXA2 knockdown cells. Moreover, ANXA2 knockdown or knockout could increase NF-κB and MAPK phosphorylation activity in response to M. bovis infection. Additionally, ANXA2 knockdown also significantly decreased the CD44 transcripts via exon V3 and V7 skipping after M. bovis infection. We concluded that M. bovis borrowed host ANXA2 to mediate its adhesion and invasion thereby negatively regulating molecular expression essential to IL-17 signal pathway. Furthermore, CD44 V3 and V7 isoforms might contribute to this ANXA2 meditated processes in M. bovis infected EBL cells. These findings revealed a new understanding of pathogenesis for M. bovis infection.

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using 99mTc-MAG3-Cet-F(ab')2-Based SPECT/CT Imaging.

Purpose: This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab')2 fragment- (Cet-F(ab')2-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models. Methods: Cet-F(ab')2 was synthesized using immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) protease and purified with protein A beads. The product and its in vitro stability in normal saline and 1% bovine serum albumin were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The EGFR expression in the human colon tumor cell line HT29 and the human stomach tumor cell line MGC803 were verified using western blotting and immunocytochemistry. Cet-F(ab')2 was conjugated with 5(6)-carboxytetramethylrhodamine succinimidyl ester to demonstrate its binding ability to the MGC803 and HT29 cells. Cet-F(ab')2 was conjugated with NHS-MAG3 for 99mTc radiolabeling. The best imaging time was determined using a biodistribution assay at 1, 4, 16, and 24 h after injection of the 99mTc-MAG3-Cet-F(ab')2 tracer. Furthermore, 99mTc-MAG3-Cet-F(ab')2 SPECT/CT was performed on MGC803 and HT29 tumor-bearing nude mice. Results: HT29 cells had low EGFR expression while MGC803 cell exhibited the high EGFR expression. Cet-F(ab')2 and intact cetuximab showed similar high binding ability to MGC803 cells but not to HT29 cells. Cet-F(ab')2 and 99mTc-MAG3-Cet-F(ab')2 showed excellent in vitro stability. The biodistribution assay showed that the target to nontarget ratio was the highest at 16 h (17.29 ± 5.72, n = 4) after tracer injection. The 99mTc-MAG3-Cet-F(ab')2-based SPECT/CT imaging revealed rapid and sustained tracer uptake in MGC803 tumors rather than in HT29 tumors with high image contrast, which was consistent with the results in vitro. Conclusion: SPECT/CT imaging using 99mTc-MAG3-Cet-F(ab')2 enables the evaluation of the EGFR expression in murine EGFR-positive tumors, indicating the potential utility for noninvasive evaluation of the EGFR expression in tumors.

Optimizing acquisition times for total-body positron emission tomography/computed tomography with half-dose 18F-fluorodeoxyglucose in oncology patients.

BACKGROUND: The present study aimed to explore the boundary of acquisition time and propose an optimized acquisition time range for total-body positron emission tomography (PET)/computed tomography (CT) oncological imaging using half-dose (1.85 MBq/kg) 18F-fluorodeoxyglucose activity based on diagnostic needs. METHODS: In this retrospective study based on a total-body PET system (uEXPLORER), an exploration cohort (October 2019-December 2019) of 46 oncology patients was first studied. The acquisition time for all patients was 15 min, and the acquired images were reconstructed and further split into 15-, 8-, 5-, 3-, 2-, and 1-min duration groups (abbreviated as G15, G8, G5, G3, G2, and G1). The image quality and lesion detectability of reconstructed PET images with different acquisition times were evaluated subjectively (5-point scale, lesion detection rate) and objectively (standardized uptake values, tumor-to-background ratio). In the same way, the initial optimized acquisition times were further validated in a cohort of 147 oncology patients (December 2019-June 2021) by using the Gs images (the images obtained using the 15- and 10-min acquisition times) as controls. RESULTS: In the exploration cohort, the subjective scores for G1, G2, G3, G5, and G8 images were 2.0 ± 0.2, 2.9 ± 0.3, 3.0 ± 0.0, 3.9 ± 0.2, and 4.2 ± 0.4, respectively. Two cases in G1 were rated as 1 point. No significant difference in scores was observed between G5 and G8 (p > 0.99). In general, groups with a longer acquisition time showed lower background uptake and lesion conspicuity. Compared with G15, lesion detection rate significantly reduced to 85.3% in G1 (p < 0.05). In the validation cohort, the subjective score was 3.0 ± 0.2 for G2, 3.0 ± 0.1 for G3, 3.6 ± 0.5 for G5, 4.0 ± 0.3 for G8, and 4.4 ± 0.5 for Gs. Only the scores between G2 and G3 were not significantly different (p > 0.99). The detection rates (204 lesions) significantly reduced to 94.1-90.2% in G3 and G2 (all p < 0.05). CONCLUSION: A 2-min acquisition time provided acceptable performance in certain groups and specific medical situations. And protocols with acquisition times ≥ 5 min could provide comparable lesion detectability as regular protocols, showing better compatibility and feasibility with clinical practice.