Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging.

BACKGROUND: The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor. RESULTS: The radiochemical yield of [68Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [68Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [68Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [68Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71. CONCLUSION: These results suggest that [68Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

Association of phthalate metabolites with periodontitis: a population-based study.

BACKGROUND: Widespread exposure to phthalates may raise the probability of various diseases. However, the association of phthalate metabolites with periodontitis remains unclear. METHODS: Totally 3402 participants from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 cycles were enrolled in the cross-sectional investigation. We utilized weighted logistic regression to evaluate the association of ten phthalate metabolites with periodontitis. Restricted cubic spline analysis was applied to investigate potential nonlinear relationships. RESULTS: The weighted prevalence of periodontitis in the study was 42.37%. A one standard deviation (SD) rise in log-transformed levels of mono-2-ethyl-5-carboxypenty phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-isobutyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP) was associated with higher odds of periodontitis, with odds ratios (95% confidence intervals) of 1.08 (1.02-1.14), 1.07 (1.02-1.11), 1.10 (1.05-1.15), 1.05 (1.01-1.09), 1.09 (1.04-1.14), and 1.08 (1.03-1.13), respectively. Individuals with the highest quartile concentrations of MECPP, MnBP, MEHHP, MEOHP, and MBzP were associated with 32%, 20%, 30%, 25%, and 26% increased odds of periodontitis, respectively, compared to those with the lowest quartile. Additionally, mono-(3-carboxypropyl) phthalate (MCPP) demonstrated an interesting inverted J-shaped relationship with periodontitis. CONCLUSIONS: The findings indicate an association of certain phthalate metabolites with periodontitis among US adults.

Left Ventricular Remodelling Associated with the Transient Elevated [68Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

BACKGROUND: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. METHODS: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. RESULTS: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). CONCLUSIONS: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.

Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study.

AIM: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis. METHODS: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed. RESULTS: The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques. CONCLUSIONS: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.

STMP and PVPA as Templating Analogs of Noncollagenous Proteins Induce Intrafibrillar Mineralization of Type I Collagen via PCCP Process.

The phosphorylated noncollagenous proteins (NCPs) play a vital role in manipulating biomineralization, while the mechanism of phosphorylation of NCPs in intrafibrillar mineralization of collagen fibril has not been completely deciphered. Poly(vinylphosphonic acid) (PVPA) and sodium trimetaphosphate (STMP) as templating analogs of NCPs induce hierarchical mineralization in cooperation with indispensable sequestration analogs such as polyacrylic acid (PAA) via polymer-induced liquid-like precursor (PILP) process. Herein, STMP-Ca and PVPA-Ca complexes are proposed to achieve rapid intrafibrillar mineralization through polyelectrolyte-Ca complexes pre-precursor (PCCP) process. This strategy is further verified effectively for remineralization of demineralized dentin matrix both in vitro and in vivo. Although STMP micromolecule fails to stabilize amorphous calcium phosphate (ACP) precursor, STMP-Ca complexes facilely permeate into intrafibrillar interstices and trigger phase transition of ACP to hydroxyapatite within collagen. In contrast, PVPA-stabilized ACP precursors lack liquid-like characteristic and crystallize outside collagen due to rigid conformation of PVPA macromolecule, while PVPA-Ca complexes infiltrate into partial intrafibrillar intervals under electrostatic attraction and osmotic pressure as evidenced by intuitionistic 3D stochastic optical reconstruction microscopy (3D-STORM). The study not only extends the variety and size range of polyelectrolyte for PCCP process but also sheds light on the role of phosphorylation for NCPs in biomineralization.

Effects of postoperative antioxidants on the salivary glands in patients with thyroid cancer undergoing radioactive iodine-131 treatment.

OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.

Overall survival and short-term efficacy analysis of cervical squamous cell carcinoma with skeletal muscle and 18F-FDG PET/CT parameters.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

Dentin surface modification by MDP to improve dentin bonding stability: Topological enhancement and mineralization of collagen structure in hybrid layers.

Decades of research have been conducted on 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) through numerous studies. The mechanisms by which its residual calcium salts benefit dentin bonding remain undetermined. The objective of the research was to investigate the role and process of remaining calcium salts in the priming procedure and their capacity for remineralization. The investigation focused on the variations in topological structure, mechanical properties, and chemical interactions between the main agent and the dentin surface. Two adhesive modes including prime-and-rinse(P&R) and prime-and-nonrinse (P&NR) utilized to evaluate the bonding performance and remineralization ability. The findings indicated that both P&R and P&NR methods could eliminate the smear-layer, uncover dentinal-tubules, and generate a textured/rough surface on the dentin. Collagen fibrils exhibited a greater presence of inorganic minerals in the P&NR mode. Compared to control group, both P&R and P&NR groups improved immediate and aging bond strength significantly (P < 0.05). AFM and 3D-STORM revealed MDP and its residual calcium salts distributed in collagen fibrils and expanded collagen matrix. In the P&NR group, TEM revealed that the dentin collagen matrix experienced some remineralization, and there was also mineralization within the collagen fibrils embedded in the bonding interface. Thus, MDP priming improved dentin bonding stability. Residual calcium salts of P&NR process can enhance topological structure of the collagen matrix and induce intrafibrillar mineralization.

Spherization indices measured by resting SPECT improve risk stratification in patients with ischemia with non-obstructive coronary artery disease (INOCA).

BACKGROUND: The prevalence of ischemia with non-obstructive coronary artery disease (INOCA) is substantial, but its risk stratification has been suboptimal. Resting SPECT myocardial perfusion imaging (MPI) could provide useful heart information including spherical indices. We aimed to evaluate the prognostic value of spherical indices in individuals with INOCA. RESULTS: During a median follow-up of 47.2 ± 20.8 months, 49 (17.2%) patients experienced major adverse cardiac events (MACE). Compared to those without MACE, those with MACE had a higher shape index (SI) (0.60 ± 0.07 vs. 0.58 ± 0.06; P = 0.028) and a lower E2 (eccentricity index calculated by the QPS) (0.81 ± 0.05 vs. 0.83 ± 0.04; P = 0.019). MACE event-free survival analysis revealed significant differences in the SI and E2 among all patients (all log-rank P < 0.01). Multivariate Cox analysis showed abnormal SI (HR: 2.73, 95% CI 1.44-5.18, P = 0.002) and E2 (HR: 1.94, 95% CI 1.08-3.48, P = 0.026) were both independent predictors for MACE when they were put into the same model, respectively. The incorporation of the SI into the baseline model demonstrated a significant improvement in the predictive accuracy for MACEs (P = 0.026), whereas E2 did not exhibit a similar improvement (P > 0.05). CONCLUSION: For patients with INOCA, spherical indices (especially the SI) were associated with long-term MACE, which could be a preferable indicator for risk stratification and prognostic prediction.

Predictive value of 18F-FDG PET/CT radiomics for EGFR mutation status in non-small cell lung cancer: a systematic review and meta-analysis.

Objective: This study aimed to evaluate the value of 18F-FDG PET/CT radiomics in predicting EGFR gene mutations in non-small cell lung cancer by meta-analysis. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and CNKI databases were searched from the earliest available date to June 30, 2023. The meta-analysis was performed using the Stata 15.0 software. The methodological quality and risk of bias of included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score criteria. The possible causes of heterogeneity were analyzed by meta-regression. Results: A total of 17 studies involving 3763 non-small cell lung cancer patients were finally included. We analyzed 17 training cohorts and 10 validation cohorts independently. Within the training cohort, the application of 18F-FDG PET/CT radiomics in predicting EGFR mutations in NSCLC demonstrated a sensitivity of 0.76 (95% CI: 0.70-0.81) and a specificity of 0.78 (95% CI: 0.74-0.82), accompanied by a positive likelihood ratio of 3.5 (95% CI:3.0-4.2), a negative likelihood ratio of 0.31 (95% CI: 0.24-0.39), a diagnostic odds ratio of 11.0 (95% CI: 8.0-16.0), and an area under the curve (AUC) of 0.84 (95% CI: 0.80-0.87). In the validation cohort, the values included a sensitivity of 0.76 (95% CI: 0.67-0.83), a specificity of 0.75 (95% CI: 0.68-0.80), a positive likelihood ratio of 3.0 (95% CI:2.4-3.8), a negative likelihood ratio of 0.32 (95% CI: 0.24-0.44), a diagnostic odds ratio of 9 (95% CI: 6-15), and an AUC of 0.82 (95% CI: 0.78-0.85). The average Radiomics Quality Score (RQS) across studies was 10.47 ± 4.72. Meta-regression analysis identifies the application of deep learning and regions as sources of heterogeneity. Conclusion: 18F-FDG PET/CT radiomics may be useful in predicting mutation status of the EGFR gene in non-small cell lung cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022385364.

Role of neuropeptides in orofacial pain: A literature review.

BACKGROUND: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system. OBJECTIVES: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain. METHODS: We review and summarise current studies related to calcitonin gene-related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control. RESULTS: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated. CONCLUSIONS: Various neuropeptides play important but distinct (pro-nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK-1, VIP mainly play proinflammatory and pro-nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.

Remineralizing effects of hydroxypropyl methylcellulose film-loaded amorphous calcium phosphate nanoprecursors on enamel artificial caries lesions.

OBJECTIVES: This study was to investigate hydroxypropyl methylcellulose (HPMC) film as a carrier for amorphous fluorinated calcium phosphate (AFCP) nanoprecursors to continuously deliver biomimetic remineralization of enamel artificial caries lesions (ACL). MATERIALS AND METHODS: The AFCP/HPMC films were comprised of 25 wt% AFCP nanoparticles and 75 wt% HPMC. They were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and biocompatibility tests. Forty enamel ACL were prepared and randomly divided into four groups (n = 10): The enamel surfaces were covered with a pure HPMC film, Tooth Mousse Plus (contains 10% CPP-ACP and 0.2% NaF), and AFCP/HPMC film, or without any things (serving as negative control). Subsequently, all samples were alternatively kept in artificial saliva and a modified pH-cycling before they were characterized by Micro-CT, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), attenuated total reflectance (ATR)-FTIR, XRD, and nanoindentation. RESULTS: After the enamel ACL was challenged by pH cycling, Tooth Mousse Plus and AFCP/HPMC film groups exhibited less lesion depth and mineral loss than the negative control and pure HPMC film groups. Additionally, the AFCP/HPMC film group revealed a highest remineralization rate of 55.34 ± 3.10 % among the all groups (p < 0.001). The SEM findings showed that the enamel ACL were densely deposited with minerals in the AFCP/HPMC film group, and the EDX results suggested a higher content of fluorine in the remineralized tissues. In particular, the AFCP/HPMC film group exhibited the best nanomechanical performance after 2 weeks of pH cycling (p < 0.05), with the hardness (H) restored from 0.29 ± 0.19 to 2.69 ± 0.70 GPa, and elastic modulus (Er) restored from 10.77 ± 5.30 to 68.83 ± 12.72 GPa. CONCLUSION: The AFCP/HPMC film might be used as a promising strategy for arresting or reversing incipient enamel caries lesions.

Manipulating HGF signaling reshapes the cirrhotic liver niche and fills a therapeutic gap in regeneration mediated by transplanted stem cells.

Long-term stem cell survival in the cirrhotic liver niche to maintain therapeutic efficacy has not been achieved. In a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis animal model, we previously showed that liver-resident stem/progenitor cells (MLpvNG2+ cells) or immune cells have improved survival in the fibrotic liver environment but died via apoptosis in the cirrhotic liver environment, and increased levels of hepatocyte growth factor (HGF) mediated this cell death. We tested the hypothesis that inhibiting HGF signaling during the cirrhotic phase could keep the cells alive. We used adeno-associated virus (AAV) vectors designed to silence the c-Met (HGF-only receptor) gene or a neutralizing antibody (anti-cMet-Ab) to block the c-Met protein in the DEN-induced liver cirrhosis mouse model transplanted with MLpvNG2+ cells between weeks 6 and 7 after DEN administration, which is the junction of liver fibrosis and cirrhosis at the site where most intrahepatic stem cells move toward apoptosis. After 4 weeks of treatment, the transplanted MLpvNG2+ cells survived better in c-Met-deficient mice than in wild-type mice, and cell activity was similar to that of the mice that received MLpvNG2+ cells at 5 weeks after DEN administration (liver fibrosis phase when most of these cells proliferated). Mechanistically, a lack of c-Met signaling remodeled the cirrhotic environment, which favored transplanted MLpvNG2+ cell expansion to differentiation into mature hepatocytes and initiate endogenous regeneration by promoting mature host hepatocyte generation and mediating functional improvements. Therapeutically, c-Met-mediated regeneration can be mimicked by anti-cMet-Ab to interfere functions, which is a potential drug for cell-based treatment of liver fibrosis/cirrhosis.

Research progress on direct pulp capping of primary teeth / 口腔疾病防治

@#The timely treatment of dental caries and pulp disease in primary teeth holds significant importance for maintaining children's oral health. Direct pulp capping (DPC) is a vital pulp treatment that involves covering the exposed pulp with bioactive materials to promote dentin bridge formation. DPC is commonly used in primary teeth with vital pulp and mechanical pulp exposure not exceeding 1 mm. DPC offers advantages such as minimal invasiveness, comfort, simplicity of operation and short chair-side time, making it suitable for pediatric dental clinical practice. Early studies suggested negative treatment outcomes for DPC in primary teeth with carious pulp exposure. Over the years, there have been advancements in materials and technology demonstrating positive outcomes in the clinical research of primary teeth with deep caries. However, due to the limited quality of related studies, DPC has not been widely recommended for the treatment of primary teeth with carious pulp exposure, and its widespread use needs further support by more high-quality evidence-based medical research. The success rate of DPC in primary teeth is influenced by factors including pulp status, clinical operations (such as isolation and caries removal), pulp capping material, cavity type, tooth position, coronal sealing, and dental fear. In clinical operation, dentists should accurately assess pulp status and minimize bacterial contamination. Mineral trioxide aggregate (MTA) is a DPC agent with relatively sufficient evidence and good therapeutic effects, and the crown should be tightly sealed after pulp capping. Additionally, the effects of novel biocompatible materials such as iRoot BP Plus used in DPC of primary teeth, and the influence of other factors like hemostatic methods on the prognosis of affected teeth, need further exploration.

Management Of Ectopic Eruption Of Bilateral Mandibular First Permanent Molars: A Case Report And Literature Review.

Ectopic eruption of the first permanent molars is a local eruption disturbance. The frequency of ectopically erupted first permanent molars is predominant in boys and primarily affects the maxilla. Interceptive treatment for irreversible ectopic eruptions should be initiated early to prevent space loss and the impaction of the second premolars. Herein, we report the case of a six-year-old girl with irreversible ectopic eruption of the bilateral mandibular first permanent molarstreated with a modified lingual arch. The mandibular first permanent molars were successfully distalised after six months of treatment, and one year of follow-up showed a satisfactory outcome. The modified lingual arch satisfies not only the clinical aspects of treatment but also the patient's well-being. However, the lingual arch may disturb tooth eruption in the mixed dentition stage.

Comparative effects of hepatocyte growth factor and tacrolimus on acute liver allograft early tolerance.

Allostimulated CD8+ T cells (aCD8+ T cells), as the main mediators of acute liver rejection (ARJ), are hyposensitive to apoptosis due to the inactivation of death receptor FAS-mediated pathways and fail to allow tolerance induction, eventually leading to acute graft rejection. Although tacrolimus (FK506), the most commonly used immunosuppressant (IS) in the clinic, allows tolerance induction, its use is limited because its target immune cells are unknown and it is associated with increased incidences of malignancy, infection, and nephrotoxicity, which substantially impact long-term liver transplantation (LTx) outcomes. The dark agouti (DA)-to-Lewis rat LTx model is a well-known ARJ model and was hence chosen for the present study. We show that both hepatocyte growth factor (HGF) (cHGF, containing the main form of promoting HGF production) and recombinant HGF (h-rHGF) exert immunoregulatory effects mainly on allogeneic aCD8+ T cell suppression through FAS-mediated apoptotic pathways by inhibiting cMet to FAS antagonism and Fas trimerization, leading to acute tolerance induction. We also showed that such inhibition can be abrogated by treatment with neutralizing antibodies against cMet (HGF-only receptor). In contrast, we did not observe these effects in rats treated with FK506. However, we observed that the effect of anti-rejection by FK506 was mainly on allostimulated CD4+ T cell (aCD4+ T cell) suppression and regulatory T cell (Treg) promotion, in contrast to the mechanism of HGF. In addition, the protective mechanism of HGF in FK506-mediated nephrotoxicity was addressed. Therefore, HGF as a tolerance inducer, whether used in combination with FK506 or as monotherapy, may have good clinical value. Additional roles of these T-cell subpopulations in other biological systems and studies in these fields will also be meaningful.

Detection of prohibited and restricted object X-ray images based on Hi color space segmentation.

BACKGROUND: X-ray imaging plays an important role in security inspection. However, the objects are complex, which makes it difficult to automatically detect prohibited and restricted objects. OBJECTIVE: This study aims to develop and test a detection method based on a new image segmentation scheme to solve the problem of detecting prohibited and restricted objects from pseudo-color X-ray images with complex backgrounds. METHODS: The internal mechanism of the influence of different color spaces on image segmentation effect is explored, and the color space component Hi is studied. Furthermore, the mechanism of the new Hi component and the influence law of its adjustable coefficient are revealed. Additionally, a detection method based on Hi color space segmentation for pseudo-color X-ray images is proposed. The segmentation and detection methods are then tested on actual X-ray images. RESULTS: The results show that hue has the greatest influence on image segmentation effect of the pseudo-color X-ray images. For different pseudo-color X-ray images with complex backgrounds, applying the proposed new Hi color space segmentation method achieves overall accuracy of 0.974 and 1.0 in detecting the gun and knife, respectively. CONCLUSION: The new X-ray image detection method based on the Hi color space segmentation proposed in this paper enables to better solve the complex background problem including object overlap and adhesion and thus more effectively meet the requirements of actual security inspection.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Comparative study of the quantitative accuracy of oncological PET imaging based on deep learning methods.

Background: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an important tool for tumor assessment. Shortening scanning time and reducing the amount of radioactive tracer remain the most difficult challenges. Deep learning methods have provided powerful solutions, thus making it important to choose an appropriate neural network architecture. Methods: A total of 311 tumor patients who underwent 18F-FDG PET/CT were retrospectively collected. The PET collection time was 3 min/bed. The first 15 and 30 s of each bed collection time were selected to simulate low-dose collection, and the pre-90s was used as the clinical standard protocol. Low-dose PET was used as input, convolutional neural network (CNN, 3D Unet as representative) and generative adversarial network (GAN, P2P as representative) were used to predict the full-dose images. The image visual scores, noise levels and quantitative parameters of tumor tissue were compared. Results: There was high consistency in image quality scores among all groups [Kappa =0.719, 95% confidence interval (CI): 0.697-0.741, P<0.001]. There were 264 cases (3D Unet-15s), 311 cases (3D Unet-30s), 89 cases (P2P-15s) and 247 cases (P2P-30s) with image quality score ≥3, respectively. There was significant difference in the score composition among all groups (χ2=1,325.46, P<0.001). Both deep learning models reduced the standard deviation (SD) of background, and increased the signal-to-noise ratio (SNR). When 8%PET images were used as input, P2P and 3D Unet had similar enhancement effect on SNR of tumor lesions, but 3D Unet could significantly improve the contrast-noise ratio (CNR) (P<0.05). There was no significant difference in SUVmean of tumor lesions compared with s-PET group (P>0.05). When 17%PET image was used as input, SNR, CNR and SUVmax of tumor lesion of 3D Unet group had no statistical difference with those of s-PET group (P>0.05). Conclusions: Both GAN and CNN can suppress image noise to varying degrees and improve image quality. However, when 3D Unet reduces the noise of tumor lesions, it can improve the CNR of tumor lesions. Moreover, quantitative parameters of tumor tissue are similar to those under the standard acquisition protocol, which can meet the needs of clinical diagnosis.