Association of imaging classification and histopathological grading in primary intraosseous meningioma of the skull.

BACKGROUND: Primary intraosseous meningioma of the skull (PIMS) is a rare type of primary extradural meningioma (PEM) involving cranial bone. The existing literature strongly suggest the importance of radiological feacures in pathological diagnosis of PIMS. Thereby, the aim of this study is to investigate the association between imaging classification and histopathological grading in PIMS. METHODS: In this retrospective study, we retrospectively analyzed the computed tomography scan/magnetic resonance imaging and pathological data pertaining to patients with pathologically proven PIMS. The association between radiological features, imaging classification, and histopathological grading was analyzed using logistic regression analysis. RESULTS: In this study, data of 25 patients with PIMS were assessed. The univariate logistic regression analysis results showed significant correlation between histopathological grading and imaging classification (OR: 22.5; 95% CI: 2.552-198.378; p = 0.005), intra- and extracalvarial extension (OR: 7.2; 95% CI: 1.066-48.639; p = 0.043), and tumor margin (OR: 7.19; 95% CI: 1.06-47.61; p = 0.043). According to the results of multivariate logistic regression analysis, imaging classification was the strongest independent risk factor for high-grade PIMS, and the risk of aggressiveness of osteoblastic type of PIMS was 16.664 times higher than that of osteolytic type of PIMS (OR: 16.664; 95% CI: 1.15-241.508; p = 0.039). CONCLUSIONS: Imaging classification is an independent risk factor for high-grade PIMS.

SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

CT-based radiomics for predicting lymph node metastasis in esophageal cancer: a systematic review and meta-analysis.

Objective: We aimed to evaluate the diagnostic effectiveness of computed tomography (CT)-based radiomics for predicting lymph node metastasis (LNM) in patients diagnosed with esophageal cancer (EC). Methods: The present study conducted a comprehensive search by accessing the following databases: PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying relevant studies published until July 10th, 2023. The diagnostic accuracy was summarized using the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). The researchers utilized Spearman's correlation coefficient for assessing the threshold effect, besides performing meta-regression and subgroup analysis for the exploration of possible heterogeneity sources. The quality assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies-2 and the Radiomics Quality Score (RQS). Results: The meta-analysis included six studies conducted from 2018 to 2022, with 483 patients enrolled and LNM rates ranging from 27.2% to 59.4%. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC, along with their corresponding 95% CI, were 0.73 (0.67, 0.79), 0.76 (0.69, 0.83), 3.1 (2.3, 4.2), 0.35 (0.28, 0.44), 9 (6, 14), and 0.78 (0.74, 0.81), respectively. The results demonstrated the absence of significant heterogeneity in sensitivity, while significant heterogeneity was observed in specificity; no threshold effect was detected. The observed heterogeneity in the specificity was attributed to the sample size and CT-scan phases (P < 0.05). The included studies exhibited suboptimal quality, with RQS ranging from 14 to 16 out of 36. However, most of the enrolled studies exhibited a low-risk bias and minimal concerns relating to applicability. Conclusion: The present meta-analysis indicated that CT-based radiomics demonstrated a favorable diagnostic performance in predicting LNM in EC. Nevertheless, additional high-quality, large-scale, and multicenter trials are warranted to corroborate these findings. Systematic Review Registration: Open Science Framework platform at https://osf.io/5zcnd.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Corydalis saxicolaBunting total alkaloid eliminates Porphyromonas gingivalis strain 33277 internalized into macrophages by inhibition of TLR2.

OBJECTIVE: This study aimed to investigate the impact of Corydalis Saxicola Bunting Total Alkaloid (CSBTA) on Porphyromonas gingivalis internalization within macrophages and explore the potential role of Toll-Like Receptor 2 (TLR2) in this process. METHODS: We established a P. gingivalis internalization model in macrophages by treating P. gingivalis-infected macrophages (MOI=100:1) with 200 µg/mL metronidazole and 300 µg/mL gentamicin for 1 h. Subsequently, the model was exposed to CSBTA at concentrations of 0.02 g/L or 1 µg/mL Pam3CSK4. After a 6 h treatment, cell lysis was performed with sterile water to quantify bacterial colonies. The mRNA expressions of TLR2 and interleukin-8 (IL-8) in macrophages were analyzed using RT-qPCR, while their protein levels were assessed via Western blot and ELISA respectively. RESULTS: P. gingivalis could internalize into macrophages and enhance the expression of TLR2 and IL-8. Activation of TLR2 by Pam3CSK4 contributed to P. gingivalis survival within macrophages and increased TLR2 and IL-8 expression. Conversely, 0.02 g/L CSBTA effectively cleared intracellular P. gingivalis, achieving a 90 % clearance rate after 6 h. Moreover, it downregulated the expression of TLR2 and IL-8 induced by P. gingivalis. However, the inhibitory effect of CSBTA on the internalized P. gingivalis model was attenuated by Pam3CSK4. CONCLUSION: CSBTA exhibited the ability to reduce the presence of live intracellular P. gingivalis and lower IL-8 expression in macrophages, possibly by modulating TLR2 activity.

Evaluating the Role of Morphological Parameters in the Prostate Transition Zone in PHI-Based Predictive Models for Detecting Gray Zone Prostate Cancer.

Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P < .05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. Conclusion: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZ-adjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions.

Effects of microplastics and cadmium on growth rate, photosynthetic pigment content and antioxidant enzymes of duckweed (Lemma minor).

Cadmium (Cd) and polyethylene (PE) seriously contaminate the aquatic environment and threaten human health. Many studies have reported the toxic effects of Cd and PE on plants, whereas few have reported the combined contamination of these two pollutants. In this study, duckweed (Lemma minor) was used as an indicator to explore the effect of PE microplastics (PE-MPs) at concentrations of 10, 50, 100, 200, and 500 mg/L on tolerance to 1 mg/L Cd. The results showed that different concentrations of PE-MPs inhibited the growth rate and chlorophyll content of duckweed to different degrees, both of which were minimal at 50 mg/L PE-MPs, 0.11 g/d, and 0.32 mg/g, respectively. The highest Cd enrichment (7.77 mg/kg) and bioaccumulation factors (94.22) of duckweed were detected when Cd was co-exposed with 50 mg/L of PE-MPs. Catalase and peroxidase activity first decreased and then increased with increasing PE-MPs concentrations, showing "hormesis effects", with minimum values of 11.47 U/g and 196.00 U/g, respectively. With increasing concentrations of PE-MPs, the effect on superoxide dismutase activity increased and then declined, peaking at 162.05 U/g, and displaying an "inverted V" trend. The amount of malondialdehyde rose with different PE-MPs concentrations. This research lay a foundation for using duckweed to purify water contaminated with MPs and heavy metals.

Transcriptomic and Functional Analyses of Two Cadmium Hyper-Enriched Duckweed Strains Reveal Putative Cadmium Tolerance Mechanisms.

Cadmium (Cd) is one of the most toxic metals in the environment and exerts deleterious effects on plant growth and production. Duckweed has been reported as a promising candidate for Cd phytoremediation. In this study, the growth, Cd enrichment, and antioxidant enzyme activity of duckweed were investigated. We found that both high-Cd-tolerance duckweed (HCD) and low-Cd-tolerance duckweed (LCD) strains exposed to Cd were hyper-enriched with Cd. To further explore the underlying molecular mechanisms, a genome-wide transcriptome analysis was performed. The results showed that the growth rate, chlorophyll content, and antioxidant enzyme activities of duckweed were significantly affected by Cd stress and differed between the two strains. In the genome-wide transcriptome analysis, the RNA-seq library generated 544,347,670 clean reads, and 1608 and 2045 differentially expressed genes were identified between HCD and LCD, respectively. The antioxidant system was significantly expressed during ribosomal biosynthesis in HCD but not in LCD. Fatty acid metabolism and ethanol production were significantly increased in LCD. Alpha-linolenic acid metabolism likely plays an important role in Cd detoxification in duckweed. These findings contribute to the understanding of Cd tolerance mechanisms in hyperaccumulator plants and lay the foundation for future phytoremediation studies.

Tinopanoids K-T, clerodane diterpenoids with anti-inflammatory activity from Tinospora crispa.

A total of 17 structurally diverse clerodane diterpenoids, including ten undescribed clerodane diterpenoids (tinopanoids K-T, 1-10) and seven known compounds (11-17), were isolated from the vines and leaves of Tinospora crispa. Compound 3 has not only bear the dominant substituents of γ-hydroxy-α, ß-unsaturated-γ-lactone with anti-inflammatory activity, but also a ternary epoxy structure at C-3/C-4. The planar structures and relative configurations of the clerodane diterpenoids were elucidated by spectroscopic data interpretation. The absolute configurations of compounds 1, 4, 8 and 13 were determined by single-crystal X-ray crystallographic, while that of compound 3 was determined using computed ECD data and single crystal X-ray diffraction of related p-bromobenzoate ester (3a). Subsequently, all compounds were evaluated for their inhibitory effect on nitric oxide (NO) production of LPS-activated BV-2 cells, and compounds 3 and 8 exhibited better NO inhibitory potency, with IC50 values of 5.6 and 13.8 µM than the positive control minocycline (Mino, IC50 = 22.9 µM). The corresponding results of western blot analysis and qRT-PCR revealed that compound 3 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions, mRNA levels of pro-inflammatory cytokins of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 1ß (IL-1ß). The underlying mechanism by which compound 3 exerted anti-neuroinflammatory effects was investigated by western blot and immunofluorescence assay, which suggested compound 3 inhibited LPS induced neuroinflammation via the suppression of toll-like receptor 4 (TLR4) dependent Signal Transducer and Activator of Transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of Heme Oxygenase-1 (HO-1) mediated signals.

Activation of AMPKα2 attenuated doxorubicin-induced cardiotoxicity via inhibiting lipid peroxidation associated ferroptosis.

Ferroptosis has been suggested to involve in doxorubicin (DOX)-induced cardiotoxicity. However, the underlying mechanisms and regulatory targets of cardiomyocyte ferroptosis remains to be understood. This study demonstrated that the up-regulation of ferroptosis associated proteins genes were accompanied with the down-regulation of AMPKα2 phosphorylation in DOX treated mouse heart or neonatal rat cardiomyocytes (NRCMs). AMPKα2 knockout (AMPKα2-/-) significantly exacerbated mouse cardiac dysfunction, increased mortality, promoting ferroptosis associated mitochondrial injuries, enhanced ferroptosis associated proteins and genes expression, and lead to accumulation of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in mouse serum and hearts respectively. Ferrostatin-1 administration markedly improved cardiac function, decreased mortality, inhibited mitochondrial injuries and ferroptosis associated proteins and genes expression, and depressed accumulation of LDH and MDA in DOX treated AMPKα2-/- mouse. Moreover, Adeno-associated virus serotype 9 AMPKα2 (AAV9-AMPKα2) or AICAR treatment mediated AMPKα2 activation could significantly improve cardiac function and depress ferroptosis in mouse. AMPKα2 activation or silence could also inhibit or promote ferroptosis associated injuries in DOX treated NRCMs respecitively. Mechanistically, AMPKα2/ACC mediated lipid metabolism has been suggested to involve in regulating DOX-treatment induced ferroptosis other than mTORC1 or autophagy dependent pathway. The metabolomics analysis exhibited that AMPKα2-/- significantly enhanced accumulation of polyunsaturated fatty acids (PFAs), oxidized lipid, and phosphatidylethanolamine (PE). Finally, this study also demonstrated that metformin (MET) treatment could inhibit ferroptosis and improve cardiac function via activating AMPKα2 phosphorylation. The metabolomics analysis exhibited that MET treatment significantly depressed PFAs accumulation in DOX treated mouse hearts. Collectively, this study suggested that AMPKα2 activation might protect against anthracycline chemotherapeutic drugs mediated cardiotoxicity via inhibiting ferroptosis.

CT values of contrast-enhanced CBBCT: A useful diagnostic tool for benign and malignant breast lesions.

BACKGROUND: Computed tomography (CT) value studies of cone-beam breast CT (CBBCT) mainly focus on the enhancement value or enhancement rate, and there has been no study on the CT value (Hounsfield units [HU]) of the lesion itself. PURPOSE: To investigate the CT values under contrast-enhanced CBBCT (CE-CBBCT) and non-contrast-enhanced CBBCT (NC-CBBCT) in scanning for the differential diagnosis of benign and malignant breast lesions. MATERIAL AND METHODS: A retrospective analysis was performed on 189 cases of mammary glandular tissues that underwent NC-CBBCT and CE-CBBCT examination. The qualitative CT values of the lesions, standardized Δ(L-A), standardized Δ*(L - G), standardized Δ(L-A) (Post 1st-Pre), and standardized Δ*(L-G) (Post 2nd-Post 1st) between the benign and malignant groups were compared. Prediction performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In total, 58 cases were included in the benign group, 79 cases were included in the malignant group, and 52 cases were included in the normal group. The best diagnostic thresholds of CT values for L (Post 1st-Pre), Δ(L-A) (Post 1st-Pre), and Δ*(L-G) (Post 1st-Pre) were 49.5, 44, and 64.8 HU, respectively. The Δ(L-A) Post-1st rate values of CBBCT had medium diagnostic efficacy (AUC = 0.74, sensitivity = 76.6%, specificity = 69.4%). CONCLUSION: CE-CBBCT can improve the diagnostic efficiency of breast lesions compared with NC-CBBCT. The CT values (HU) of lesions do not need to be standardized with fat and can be directly used in clinical differential diagnosis. The first contrast phase (60 s) is recommended to reduce the radiation exposure.

Cryptotanshinone Attenuated Pathological Cardiac Remodeling In Vivo and In Vitro Experiments.

Objective: Cardiac remodeling has been demonstrated to be the early stage and common pathway for various types of cardiomyopathy, but no specific treatment has been suggested to prevent its development and progress. This study was aimed at assessing whether Cryptotanshinone (CTS) treatment could effectively attenuate cardiac remodeling in vivo and in vitro. Methods: Aortic banding (AB) surgery was performed to establish a pressure-overload-induced mouse cardiac remodeling model. Echocardiography and pressure-volume proof were used to examine mouse cardiac function. Hematoxylin and eosin (HE) and Picro-Sirius Red (PSR) staining were used to assess cardiac remodeling in vivo. Mouse hearts were collected to analysis signaling pathway and cardiac remodeling markers, respectively. Furthermore, neonatal rat cardiomyocyte (NRCMs) and cardiac fibroblast (CF) were isolated to investigate the roles and mechanisms of CTS treatment in vitro. Results: CTS administration significantly alleviated pressure-overload-induced mouse cardiac dysfunction, inhibited cardiac hypertrophy, and reduced cardiac fibrosis. Mechanically, CTS treatment significantly inhibited the STAT3 and TGF-ß/SMAD3 signaling pathways. In vitro experiments, CTS treatment markedly inhibited AngII-induced cardiomyocyte hypertrophy and TGF-ß-induced myofibroblast activation via inhibiting STAT3 phosphorylation and its nuclear translocation. Finally, CTS treatment could not protect against pressure overload-induced mouse cardiac remodeling after adenovirus-associated virus (AAV)9-mediated STAT3 overexpression in mouse heart. Conclusion: CTS treatment might attenuate pathological cardiac remodeling via inhibiting STAT3-dependent pathway.

Influence of cadmium and microplastics on physiological responses, ultrastructure and rhizosphere microbial community of duckweed.

The combined contamination of heavy metals and microplastics is widespread in freshwater environments. However, there are few researches on their combined effects on aquatic plants. In this study, the effects of single and combined stress of 0.01 mg L-1 cadmium (Cd), 50 mg L-1 polyethylene and 50 mg L-1 polypropylene for 15 days on the physiological response, ultrastructure and rhizosphere microbial community of duckweed were investigated. The results showed that Cd and microplastics single or combined stress inhibited the growth of duckweed, shortened the root length and decreased the chlorophyll content. Compared with single Cd treatments, the combination of microplastics and Cd increased duckweed growth rate and increased superoxide dismutase activity and malondialdehyde content and reduced chloroplast structural damage, indicating that the combined stress could reduce the toxicity of heavy metals to duckweed. Through the study of rhizosphere microbial diversity, 1381 Operational Taxonomic Unit (OTUs) were identified and rich microbial communities were detected in the duckweed rhizosphere. Among them, the main microbial communities were Proteobacteria, Bacteroidetes, and Cyanobacteria. Compared with Cd single stress, the ACE and chao index of rhizosphere microbial community increased under combined stress, indicating that the diversity and abundance of microbial communities were improved after combined stress treatment. Our study revealed the effects of heavy metals and microplastics on aquatic plants, providing a theoretical basis for duckweed applications in complex water pollution.

MRI-based random survival Forest model improves prediction of progression-free survival to induction chemotherapy plus concurrent Chemoradiotherapy in Locoregionally Advanced nasopharyngeal carcinoma.

BACKGROUND: The present study aimed to explore the application value of random survival forest (RSF) model and Cox model in predicting the progression-free survival (PFS) among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT). METHODS: Eligible LANPC patients underwent magnetic resonance imaging (MRI) scan before treatment were subjected to radiomics feature extraction. Radiomics and clinical features of patients in the training cohort were subjected to RSF analysis to predict PFS and were tested in the testing cohort. The performance of an RSF model with clinical and radiologic predictors was assessed with the area under the receiver operating characteristic (ROC) curve (AUC) and Delong test and compared with Cox models based on clinical and radiologic parameters. Further, the Kaplan-Meier method was used for risk stratification of patients. RESULTS: A total of 294 LANPC patients (206 in the training cohort; 88 in the testing cohort) were enrolled and underwent magnetic resonance imaging (MRI) scans before treatment. The AUC value of the clinical Cox model, radiomics Cox model, clinical + radiomics Cox model, and clinical + radiomics RSF model in predicting 3- and 5-year PFS for LANPC patients was [0.545 vs 0.648 vs 0.648 vs 0.899 (training cohort), and 0.566 vs 0.736 vs 0.730 vs 0.861 (testing cohort); 0.556 vs 0.604 vs 0.611 vs 0.897 (training cohort), and 0.591 vs 0.661 vs 0.676 vs 0.847 (testing cohort), respectively]. Delong test showed that the RSF model and the other three Cox models were statistically significant, and the RSF model markedly improved prediction performance (P < 0.001). Additionally, the PFS of the high-risk group was lower than that of the low-risk group in the RSF model (P < 0.001), while comparable in the Cox model (P > 0.05). CONCLUSION: The RSF model may be a potential tool for prognostic prediction and risk stratification of LANPC patients.

A Clinical-Radiomics Nomogram Based on Magnetic Resonance Imaging for Predicting Progression-Free Survival After Induction Chemotherapy in Nasopharyngeal Carcinoma.

Purpose: This paper aimed to establish and verify a radiomics model based on magnetic resonance imaging (MRI) for predicting the progression-free survival of nasopharyngeal carcinoma (NPC) after induction chemotherapy (IC). Materials and Methods: This cohort consists of 288 patients with clinical pathologically confirmed NPC, which was collected from January 2015 to December 2018. All NPC patients were randomly divided into two cohorts: training (n=202) and validation (n=86). Radiomics features from the MRI images of NPC patients were extracted and selected before IC. The patients were classified into high- and low-risk groups according to the median of Radscores. The significant imaging features and clinical variables in the univariate analysis were constructed for progression-free survival (PFS) using the multivariate Cox regression model. A survival analysis was performed using Kaplan-Meier with log-rank test and then each model's stratification ability was evaluated. Results: Epstein-Barr virus (EBV) DNA before treatment was an independent predictor for PFS (p < 0.05). Based on the pyradiomic platform, we extracted 1,316 texture parameters in total. Finally, 16 texture features were used to build the model. The clinical radiomics-based model had good prediction capability for PFS, with a C-index of 0.827. The survival curve revealed that the PFS of the high-risk group was poorer than that of the low-risk group. Conclusion: This research presents a nomogram that merges the radiomics signature and the clinical feature of the plasma EBV DNA load, which may improve the ability of preoperative prediction of progression-free survival and facilitate individualization of treatment in NPC patients before IC.

Contrast-Enhanced Cone-Beam Breast CT: An Analysis of Diagnostic Value in Predicting Breast Lesion With Rim Enhancement Malignancy.

Background: The objective of the current study was to investigate the diagnostic value of contrast-enhanced cone-beam breast computed tomography (CE-CBBCT) for breast lesion with rim enhancement (RE). Methods: All 36 patients were examined by non-contrast (NC-CBBCT) and contrast-enhanced CBBCT (CE-CBBCT) after contrast media (CM) injection. Qualitative morphological enhancement parameters and quantitative enhancement parameters were compared between malignant and benign groups. Multivariable logistic regression analysis was performed to identify independent factors that could predict breast lesion with RE malignancy. Receiver operating curve (ROC) was used to evaluate prediction performance. Results: A total of 36 patients with 40 lesions underwent breast CE-CBBCT were enrolled. There were significant differences in most qualitative morphological enhancement parameters between the two groups. A multivariate logistic regression model showed that △standardized HU (INRphase 2-INRpreCM) [odds ratio (OR) = 1.148, 95% CI = 1.034-1.276, p = 0.01] and △standardized HU (RPphase 2 - RPphase 1) (OR = 0.891, 95% CI = 0.814-0.976, p = 0.013) were independent indicators in predicting breast lesion with RE malignancy. △standardized HU (INRphase 2 - INRpreCM) combined with △standardized HU (RPphase 2 - RPphase 1) showed significant larger area under the receiver operating curve (AUC) and higher sensitivity than each alone (p < 0.001, AUC = 0.932, sensitivity = 92.59%, specificity = 92.31%). The regression equation of the prediction model was as follows: Logit (p) = 0.351 + 0.138X × â–³standardized HU (INRphase 2 - INRpreCM) - 0.115 × â–³standardized HU (RPphase 2 - RPphase 1). Conclusion: With the observation of qualitative morphological enhancement parameters and the comparison of quantitative enhancement parameters of CBBCT, a reliable basis for the diagnostic accuracy in predicting breast lesion with RE could be provided. These conclusions should be verified in large, well-designed studies.

Liquiritin Attenuates Pathological Cardiac Hypertrophy by Activating the PKA/LKB1/AMPK Pathway.

Background: Liquiritin (LQ) is one of the main flavonoids extracted from the roots of Glycyrrhiza spp., which are widely used in traditional Chinese medicine. Studies in both cellular and animal disease models have shown that LQ attenuates or prevents oxidative stress, inflammation, and apoptosis. However, the potential therapeutic effects of LQ on pressure overload-induced cardiac hypertrophy have not been so far explored. Therefore, we investigated the cardioprotective role of LQ and its underlying mechanisms in the aortic banding (AB)-induced cardiac hypertrophy mouse model. Methods and Results: Starting 3 days after AB surgery, LQ (80 mg/kg/day) was administered daily over 4 weeks. Echocardiography and pressure-volume loop analysis indicated that LQ treatment markedly improved hypertrophy-related cardiac dysfunction. Moreover, hematoxylin and eosin, picrosirius red, and TUNEL staining showed that LQ significantly inhibited cardiomyocyte hypertrophy, interstitial fibrosis, and apoptosis. Western blot assays further showed that LQ activated LKB1/AMPKα2/ACC signaling and inhibited mTORC1 phosphorylation in cardiomyocytes. Notably, LQ treatment failed to prevent cardiac dysfunction, hypertrophy, and fibrosis in AMPKα2 knockout (AMPKα2-/-) mice. However, LQ still induced LKB1 phosphorylation in AMPKα2-/- mouse hearts. In vitro experiments further demonstrated that LQ inhibited Ang II-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) by increasing cAMP levels and PKA activity. Supporting the central involvement of the cAMP/PKA/LKB1/AMPKα2 signaling pathway in the cardioprotective effects of LQ, inhibition of Ang II-induced hypertrophy and induction of LKB1 and AMPKα phosphorylation were no longer observed after inhibiting PKA activity. Conclusion: This study revealed that LQ alleviates pressure overload-induced cardiac hypertrophy in vivo and inhibits Ang II-induced cardiomyocyte hypertrophy in vitro via activating cAMP/PKA/LKB1/AMPKα2 signaling. These findings suggest that LQ might be a valuable adjunct to therapeutic approaches for treating pathological cardiac remodeling.

Neutrophil degranulation and myocardial infarction.

Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Video abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP-8, MMP-9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP-8); Matrix metalloproteinase 9 (MMP-9).

Alternative autophagy: mechanisms and roles in different diseases.

As an important mechanism to maintain cellular homeostasis, autophagy exerts critical functions via degrading misfolded proteins and damaged organelles. Recent years, alternative autophagy, a new type of autophagy has been revealed, which shares similar morphology with canonical autophagy but is independent of Atg5/Atg7. Investigations on different diseases showed the pivotal role of alternative autophagy during their physio-pathological processes, including heart diseases, neurodegenerative diseases, oncogenesis, inflammatory bowel disease (IBD), and bacterial infection. However, the studies are limited and the precise roles and mechanisms of alternative autophagy are far from clear. It is necessary to review current research on alternative autophagy and get some hint in order to provide new insight for further study. Video Abstract.