Beyond transcription, aryl hydrocarbon receptor plays a protective role in periodontitis by interacting with CaMKII.

BACKGROUND: The aryl hydrocarbon receptor (AhR) has been studied as an intracellular pattern recognition receptor that can identify bacterial pigments. To identify a potential therapeutic target for periodontitis, we investigated the expression of AhR in periodontitis and its role in the pathogenesis of periodontitis. METHODS: First, we analyzed AhR expression in a single-cell dataset from human periodontal tissue. Quantitative polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry were used to verify the AhR level. Later, we determined the phenotypes of ligature-induced periodontitis in myeloid-specific AhR-deficient mice (Lyz2-Cre+/- AhRfx/fx), after which RNA sequencing (RNA-seq), qPCR, Western blot, immunofluorescence, and immunohistochemistry were used to investigate the impacts of AhR on periodontitis and its mechanism. Finally, we determined the therapeutic effect of AhR agonist 6-Formylindolo[3,2-b]carbazole (FICZ) administration on murine periodontitis and verified the effects of FICZ on macrophage polarization in vitro. RESULTS: AhR expression was enhanced in macrophages from periodontitis patients. Deletion of AhR from macrophages aggravated ligature-induced periodontitis and promoted the inflammatory response. Calcium/calmodulin-stimulated protein kinase II (CaMKII) phosphorylation was accelerated in AhR-deficient macrophages. Inhibiting CaMKII phosphorylation ameliorated periodontitis in Lyz2-Cre+/- AhRfx/fx mice. FICZ treatment blocked alveolar bone loss and relieved periodontal inflammation. FICZ diminished M1 macrophage polarization and promoted M2 macrophage polarization upon M1 macrophage induction. CONCLUSION: AhR played a protective role in the pathogenesis of periodontitis by orchestrating macrophage polarization via interacting with the CaMKII signaling pathway.

Prediction of Subsequent Vertebral Fracture After Acute Osteoporotic Fractures from Clinical and Paraspinal Muscle Features.

To construct a nomogram based on clinical factors and paraspinal muscle features to predict vertebral fractures occurring after acute osteoporotic vertebral compression fracture (OVCF). We retrospectively enrolled 307 patients with acute OVCF between January 2013 and August 2022, and performed magnetic resonance imaging of the L3/4 and L4/5 intervertebral discs (IVDs) to estimate the cross-sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles. We also collected clinical and radiographic data. We used univariable and multivariable Cox proportional hazards models to identify factors that should be included in the predictive nomogram. Post-OVCF vertebral fracture occurred within 3, 12, and 24 months in 33, 69, and 98 out of the 307 patients (10.8%, 22.5%, and 31.9%, respectively). Multivariate analysis revealed that this event was associated with percutaneous vertebroplasty treatment, higher FI at the L3/4 IVD levels of the psoas muscle, and lower relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. Area under the curve values for subsequent vertebral fracture at 3, 12, and 24 months were 0.711, 0.724, and 0.737, respectively, indicating remarkable accuracy of the nomogram. We developed a model for predicting post-OVCF vertebral fracture from diagnostic information about prescribed treatment, FI at the L3/4 IVD levels of the psoas muscle, and relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. This model could facilitate personalized predictions and preventive strategies.

Fatty Infiltration of Multifidus Muscles: An Easily Overlooked Risk Factor for the Severity of Osteoporotic Vertebral Fractures.

OBJECTIVES: Osteoporotic vertebral fractures (OVFs) are a critical public health concern requiring urgent attention, and severe OVFs impose substantial health and economic burdens on patients and society. Analysis of the risk factors for severe OVF is imperative to actively prevent the occurrence of this degenerative disorder. This study aimed to investigate the risk factors associated with the severity of OVF, with a specific focus on changes in the paraspinal muscles. METHODS: A total of 281 patients with a first-time single-level acute OVF between January 2016 and January 2023 were enrolled in the study. Clinical and radiological data were collected and analyzed. The cross-sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles, including the multifidus muscles (MFMs), erector spinae muscles (ESMs), and psoas major muscles (PSMs), were measured by magnetic resonance imaging (MRI) of the L4/5 intervertebral discs. According to the classification system of osteoporotic fractures (OF classification) and recommended treatment plan, OVFs were divided into a low-grade OF group and a high-grade OF group. Univariate and multivariate logistic regression analyse s were performed to identify risk factors associated with the severity of OVF. RESULTS: Ninety-eight patients were included in the low-grade OF group, and 183 patients were included in the high-grade OF group. Univariate analysis revealed a significantly higher incidence of a high degree of FI of MFMs (OR = 1.71, p = 0.002) and ESMs (OR = 1.56, p = 0.021) in the high-grade OF group. Further multivariate logistic regression analysis demonstrated that a high degree of FI of the MFMs (OR = 1.71, p = 0.002) is an independent risk factor for the severity of OVF. CONCLUSION: A high degree of FI of the MFMs was identified as an independent risk factor for the severity of OVF. Decreasing the degree of FI in the MFMs might lower the incidence of the severity of OVF, potentially reducing the necessity for surgical intervention in OVF patients.

Deep learning-based artificial intelligence model for classification of vertebral compression fractures: A multicenter diagnostic study.

Objective: To develop and validate an artificial intelligence diagnostic system based on X-ray imaging data for diagnosing vertebral compression fractures (VCFs). Methods: In total, 1904 patients who underwent X-ray at four independent hospitals were retrospectively (n=1847) and prospectively (n=57) enrolled. The participants were separated into a development cohort, a prospective test cohort and three external test cohorts. The proposed model used a transfer learning method based on the ResNet-18 architecture. The diagnostic performance of the model was evaluated using receiver operating characteristic curve (ROC) analysis and validated using a prospective validation set and three external sets. The performance of the model was compared with three degrees of musculoskeletal expertise: expert, competent, and trainee. Results: The diagnostic accuracy for identifying compression fractures was 0.850 in the testing set, 0.829 in the prospective set, and ranged from 0.757 to 0.832 in the three external validation sets. In the human and deep learning (DL) collaboration dataset, the area under the ROC curves(AUCs) in acute, chronic, and pathological compression fractures were as follows: 0.780, 0.809, 0.734 for the DL model; 0.573, 0.618, 0.541 for the trainee radiologist; 0.701, 0.782, 0.665 for the competent radiologist; 0.707,0.732, 0.667 for the expert radiologist; 0.722, 0.744, 0.610 for the DL and trainee; 0.767, 0.779, 0.729 for the DL and competent; 0.801, 0.825, 0.751 for the DL and expert radiologist. Conclusions: Our study offers a high-accuracy multi-class deep learning model which could assist community-based hospitals in improving the diagnostic accuracy of VCFs.

Deep learning-based diagnosis of osteoblastic bone metastases and bone islands in computed tomograph images: a multicenter diagnostic study.

OBJECTIVE: To develop and validate a deep learning (DL) model based on CT for differentiating bone islands and osteoblastic bone metastases. MATERIALS AND METHODS: The patients with sclerosing bone lesions (SBLs) were retrospectively included in three hospitals. The images from site 1 were randomly assigned to the training (70%) and intrinsic verification (10%) datasets for developing the two-dimensional (2D) DL model (single-slice input) and "2.5-dimensional" (2.5D) DL model (three-slice input) and to the internal validation dataset (20%) for evaluating the performance of both models. The diagnostic performance was evaluated using the internal validation set from site 1 and additional external validation datasets from site 2 and site 3. And statistically analyze the performance of 2D and 2.5D DL models. RESULTS: In total, 1918 SBLs in 728 patients in site 1, 122 SBLs in 71 patients in site 2, and 71 SBLs in 47 patients in site 3 were used to develop and test the 2D and 2.5D DL models. The best performance was obtained using the 2.5D DL model, which achieved an AUC of 0.996 (95% confidence interval [CI], 0.995-0.996), 0.958 (95% CI, 0.958-0.960), and 0.952 (95% CI, 0.951-0.953) and accuracies of 0.950, 0.902, and 0.863 for the internal validation set, the external validation set from site 2 and site 3, respectively. CONCLUSION: A DL model based on a three-slice CT image input (2.5D DL model) can improve the prediction of osteoblastic bone metastases, which can facilitate clinical decision-making. KEY POINTS: • This study investigated the value of deep learning models in identifying bone islands and osteoblastic bone metastases. • Three-slice CT image input (2.5D DL model) outweighed the 2D model in the classification of sclerosing bone lesions. • The 2.5D deep learning model showed excellent performance using the internal (AUC, 0.996) and two external (AUC, 0.958; AUC, 0.952) validation sets.

Comparison of whole-body 18F-FDG PET/CT and PET/MRI for distant metastases in patients with malignant tumors: a meta-analysis.

BACKGROUND: As a first-line imaging modality, whole-body fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET/magnetic resonance imaging (MRI) had been widely applied in clinical practice. However, 18F-FDG PET/MRI may be superior to PET/CT for the diagnosis of distant metastases in patients with advanced-stage. Therefore, it is timely and important to systematically determine the diagnostic accuracy of 18F-FDG PET/MRI compared with that of 18F-FDG PET/CT for the diagnosis of distant metastases. METHODS: This study aimed to compare the diagnostic accuracy of 18F-FDG PET/CT and PET/MRI for the diagnosis of distant metastases in patients with malignant tumors. Relevant studies using both 18F-FDG PET/CT and PET/MRI for assessment of distant metastases in patients with malignant tumors were searched in PubMed, Embase, The Cochrane Library, and Scopus from January 2010 to November 2023. Two reviewers independently selected studies according to the inclusion and exclusion criteria. A reviewer extracted relevant data and assessed the quality of the eligible studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the summary receiver operating characteristic curve (AUC) for 18F-FDG PET/CT and PET/MRI were analyzed. Subgroup analysis was performed. RESULTS: Across 14 studies (1042 patients), 18F-FDG PET/MRI had a higher sensitivity (0.87 versus 0.81), AUC value (0.98 versus 0.95), and similar specificity (0.97 versus 0.97), than PET/CT for detecting distant metastases. In 3 studies of breast cancer (182 patients), 18F-FDG PET/MRI had a higher sensitivity (0.95 versus 0.87) and specificity (0.96 versus 0.94) than PET/CT. In 5 studies of lung cancer (429 patients), 18F-FDG PET/CT had a higher sensitivity (0.87 versus 0.84) and a lower specificity (0.95 versus 0.96) to PET/MRI. CONCLUSIONS: 18F-FDG PET/MRI and PET/CT both performed well as detectors of distant metastases in patients with malignant tumors, and the former has higher sensitivity. The subgroup analysis highlights that 18F-FDG PET/MRI and PET/CT hold different advantages for distant metastases staging in different tumors, PET/MRI has a higher accuracy in patients with breast cancer patients, while PET/CT has a higher accuracy in patients with lung cancer.

Overuse wrist injuries in adolescent platform and springboard divers.

To investigate overuse wrist injuries in adolescent divers using magnetic resonance imaging (MRI). The bilateral wrists (76 wrists) of 38 professional divers were examined by MRI; 42 wrists with pain were placed in the symptomatic group, and 34 wrists without pain were placed in the asymptomatic group. Two experienced radiologists assessed the wrist injuries. Chi­square test was used to compare the difference in injuries between the two groups. Subchondral osteosclerosis was observed in 47.62% of symptomatic wrists and 52.94% of asymptomatic wrists. Distal radial epiphyseal plate injury was detected in 42.86% of symptomatic wrists and 11.76% of asymptomatic wrists. Triangular fibrocartilage complex injury was observed in 19.04% of symptomatic wrists and 8.82% of asymptomatic wrists. Bursae around the wrist were observed in 21.42% of symptomatic wrists and 17.64% of asymptomatic wrists. The incidence of distal radial epiphyseal plate injury was higher in the symptomatic group than in the asymptomatic group (P = 0.007), however, other injuries were not statistically different between the two groups (P > 0.05). This study demonstrated that adolescent divers had various wrist injuries, and distal radial epiphyseal plate injury was more common in the symptomatic wrist; these injuries show no specific clinical symptoms and are easily overlooked.

MTHFR C677T polymorphism and cerebrovascular lesions in elderly patients with CSVD: A correlation analysis.

Plasma homocysteine (Hcy) has been identified as a potential risk factor for cerebral small vessel disease. Cerebral small vessel disease (CSVD) leads to cognitive impairment, depression, and other symptoms and is a common disease in middle-aged and elderly people. To investigate the relationship between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and CSVD in elderly patients, plasma levels of homocysteine (Hcy) and MTHFR genotyping were assessed. MRI and MRA were performed at the same time to analyze the relationship between different genotypes and cerebrovascular lesions. We showed that Hcy plasma levels in the TT group were significantly higher than those in the CC and CT groups. Moreover, we observed that the severity of white matter lesions was associated with women and positively correlated with age, previous coronary heart disease, luminal infarction, and MTHFR polymorphism. The multivariate logistic regression analysis showed that age, TT genotype, and lacunar infarction were independent risk factors for white matter hyperintensity (WMH). Importantly, we showed that there was a significant correlation between Hcy plasma levels and MTHFR gene polymorphism, with the TT genotype constituting an independent risk factor for WMH. Therefore, we recommended early detection of MTHFR gene polymorphisms with concomitant early intervention concerning risk factors to delay the occurrence of cognitive impairment in CSVD elderly patients.

High expression of aryl hydrocarbon receptor (AhR) plays an important role in the formation of fibrous epulis.

OBJECTIVES: Epulis is considered to be a massive reactive lesion rather than a true neoplasia. AhR is thought to be associated with inflammation and development of neoplasms. Here, we aimed to observe the expression of AhR in fibrous epulis and explore its role and possible mechanism in the pathogenesis of epulis. MATERIALS AND METHODS: Epulis and normal gingival tissues were collected, and AhR expression was detected at the mRNA and protein levels by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. The expression levels of proinflammatory cytokines and apoptosis-related factor genes in human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs) transfected with AhR short interfering RNA (siRNA) or negative control siRNA, upon stimulation with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS), were then examined. Finally, the expression levels of the proinflammatory cytokines and apoptosis-related factor genes in the epulis tissues were observed by qPCR. RESULTS: AhR expression in fibrous epulis was significantly increased at both the mRNA and protein levels. The expression of proinflammatory cytokines and apoptosis-related factor genes in hPDLCs transfected with AhR siRNA was significantly decreased when stimulated with Pg-LPS. The same trends were observed for hGFs. The opposite trend was detected in the epulis tissues. CONCLUSION: AhR may be a key factor in fibrous epulis pathogenesis that acts by regulating the expression of BCL2 family genes and inflammatory factor-related genes.

Diagnostic Performance of Diffusion-Weighted Imaging for Differentiating Malignant From Benign Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: A systematic search of articles investigating the diagnostic performance of DWI for prediction of malignant potential in IPMNs was conducted from PubMed, Embase, and Web of Science from January 1997 to 10 February 2020. QUADAS-2 tool was used to evaluate the study quality. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and their 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic (SROC) curve was then plotted, and meta-regression was also performed to explore the heterogeneity. RESULTS: Five articles with 307 patients were included. The pooled sensitivity and specificity of DWI were 0.74 (95% CI: 0.65, 0.82) and 0.94 (95% CI: 0.78, 0.99), in evaluating the malignant potential of IPMNs. The PLR was 13.5 (95% CI: 3.1, 58.7), the NLR was 0.27 (95% CI: 0.20, 0.37), and DOR was 50.0 (95% CI: 11.0, 224.0). The area under the curve (AUC) of SROC curve was 0.84 (95% CI: 0.80, 0.87). The meta-regression showed that the slice thickness of DWI (p = 0.02) and DWI parameter (p= 0.01) were significant factors affecting the heterogeneity. CONCLUSIONS: DWI is an effective modality for the differential diagnosis between benign and malignant IPMNs. The slice thickness of DWI and DWI parameter were the main factors influencing diagnostic specificity.

Refracture of the cemented vertebrae after percutaneous vertebroplasty: risk factors and imaging findings.

BACKGROUND: To determine the related imaging findings and risk factors to refracture of the cemented vertebrae after percutaneous vertebroplasty (PVP) treatment. METHODS: Patients who were treated with PVP for single vertebral compression fractures (VCFs) and met this study's inclusion criteria were retrospectively reviewed from January 2012 to January 2019. The follow-up period was at least 2 years. Forty-eight patients with refracture of the cemented vertebrae and 45 non-refractured patients were included. The following variates were reviewed: age, sex, fracture location, bone mineral density (BMD), intravertebral cleft (IVC), kyphotic angle (KA), wedge angle, endplate cortical disruption, cement volume, surgical approach, non-PMMA-endplate-contact (NPEC), cement leakage, other vertebral fractures, reduction rate (RR), and reduction angle (RA). Multiple logistic regression modeling was used to identify the independent risk factors of refracture. RESULTS: Refracture was found in 48 (51.6%) patients. Four risk factors, including IVC (P = 0.005), endplate cortical disruption (P = 0.037), larger RR (P = 0.007), and NPEC (P = 0.006) were found to be significant independent risk factors for refracture. CONCLUSIONS: Patients with IVC or larger RR, NPEC, or endplate cortical disruption have a high risk of refracture in the cemented vertebrae after PVP.

Glyburide Regulates UCP1 Expression in Adipocytes Independent of KATP Channel Blockade.

Identification of safe and effective compounds to increase or activate UCP1 expression in brown or white adipocytes remains a potent therapeutic strategy to combat obesity. Here we reported that, glyburide, one of the FDA-approved drugs currently used to treat type 2 diabetes, can significantly enhance UCP1 expression in both brown and white adipocytes. Glyburide-fed mice exhibited a clear resistance to high-fat diet-induced obesity, reduced blood triglyceride level, and increased UCP1 expression in brown adipose tissue. Moreover, in situ injection of glyburide to inguinal white adipose tissue remarkably enhanced UCP1 expression and increased thermogenesis. Further mechanistic studies indicated that the glyburide effect in UCP1 expression in adipocytes was KATP channel independent but may involve the regulation of the Ca2+-Calcineurin-NFAT signal pathway. Overall, our findings revealed the significant effects of glyburide in regulating UCP1 expression and thermogenesis in adipocytes, which can be potentially repurposed to treat obesity.

Diagnostic performance of whole-lesion apparent diffusion coefficient histogram analysis metrics for differentiating benign and malignant breast lesions: a systematic review and diagnostic meta-analysis.

BACKGROUND: Although whole-lesion apparent diffusion coefficient (ADC) histogram has been increasingly used for breast lesions, it has not been routinely used in clinical practice as an emergent promising imaging tool. PURPOSE: To evaluate the performance of whole-lesion ADC histogram analysis metrics for differentiating benign and malignant breast lesions. MATERIAL AND METHODS: A systematic PubMed/EMBASE/Cochrane electronic database search was performed for original diagnostic studies from 1 January 1970 to 2 January 2019. Summary estimates of diagnostic accuracy were generated and meta-regression was performed to explore sources of heterogeneity according to study and magnetic resonance imaging characteristics. RESULTS: Five original articles involving 493 patients were included in the meta-analysis. The pooled sensitivity and specificity of whole-lesion ADC histogram analysis were 0.85 (95% confidence interval [CI] = 0.81-0.89) and 0.79 (95% CI = 0.72-0.84) for distinguishing benign and malignant breast lesions, respectively. The area under the curve (AUC) was 0.9178. No publication bias was detected (P = 0.51). In subgroup analysis, the summary sensitivity and specificity of 50th percentile ADC value were 0.81 (95% CI = 0.71-0.88) and 0.86 (95% CI = 0.74-0.94), respectively. Meta-regression analysis indicated no covariates were sources of heterogeneity (P > 0.05). CONCLUSION: Whole-lesion ADC histogram analysis demonstrated good diagnostic performance for differentiating between benign and malignant breast lesions, with 50th percentile ADC value showing higher diagnostic accuracy than other histogram parameters. Given the limited number of studies included in the analysis, the findings from our meta-analysis will need further confirmation in future research.

MRI and histologic analysis of collagen type II sponge on repairing the cartilage defects of rabbit knee joints.

There are limited treatment options for cartilage defects in clinical practice because of the lack of suitable biomaterials. Here, we evaluated the effects of collagen type II sponge on the articular cartilage repairing process using a cartilage injury of a rabbit knee joint model. We showed that the home-made collagen type II sponges appeared to have a suitable pore size of 93.26 ± 38.4 µm for chondrocyte growth. MRI with H&E staining results demonstrated that the effusion absorption in the collagen type II sponge treated group was quicker than that of the control group. Moreover, sporadic cartilage signals first appeared at 6 weeks in the collagen type II sponge treated group. Safranin O staining and immunohistochemical analysis confirmed that the newly formed cartilage expresses glycosaminoglycan and type II collagen matrix. Using Sirius red polarized light staining, we showed that the newly formed cartilage-like areas from the collagen type II treated group are significantly greater than those of the control group. Taken together, our data demonstrated that the home-made collagen type II sponge is able to promote cartilage repair in the cartilage injury of a rabbit knee joint model.