Research on the mechanism of coal wall fragmentation and dust production characteristics in the perspective of differentiated discrete elements.

In order to efficiently and accurately control coal dust pollution in coal mining faces, this study addresses the insufficient research on the dust generation mechanism during cutting. Firstly, a similar experimental platform for simulating coal wall cutting with a drum cutter was used to investigate the changes in coal wall fragmentation and dust generation at drum speeds of 35 r/min, 50 r/min, 65 r/min, and 80 r/min. The experimental results revealed that the degree of coal wall fragmentation and dust generation increased with the increase in rotational speed, leading to a wider range of particle size distribution and an increase in the generation of fine dust particles. A 1:1 scale discrete element simulation of coal wall cutting with a drum cutter was conducted based on the experiments. The results indicated that, under the four rotational speeds, the cracks generated during coal wall fracture were predominantly tensile cracks, accounting for over 76% of the total crack count. The total number of cracks increased from 10,600 to 11,200, the number of free single particles increased from 2555 to 2728, and the fragmentation volume increased from 0.021607 to 0.023024 m3. The range and degree of coal wall fragmentation increased with the increase in drum speed.

Dynamic multifractal characteristics of acoustic emission about composite samples with different stress loading and unloading conditions.

Studying the failure characteristics of the common composite strata structure in western China is essential for evaluating stope stability and predicting coal mine dynamic disasters. To investigate the influence of different stress loading and unloading conditions on the instability characteristics of composite samples, three triaxial loading and unloading test schemes simulating different in-situ mining depths were designed. Complex triaxial tests were conducted on 12 sets of composite samples, and the bearing capacity, acoustic emission (AE) parameters and dynamic multifractal characteristics of the samples under different stress loading or unloading conditions were analyzed. The results indicate that samples tested by stress schemes simulating greater mining depths exhibit less damage, and the failure mode is a tensile-shear mixed failure, but the tensile failure is the main failure mode. The multifractal spectral parameters Δ α of AE time series during the failure of composite samples tested with triaxial loading and unloading schemes simulating different mining depths show a decreasing trend in Δ α values with increasing mining depth, while the change rules of Δ f α values are the opposite. The multifractal parameter changes degree in four-layer rock structure composite samples under different stress conditions are lower than those in three-layer rock structure composite samples, indicating that the microcrack propagation process in the three-layer composite sample is more complex, resulting in higher levels of damage. The dynamic change of multifractal parameters Δ α and Δ f α during different stress loading and unloading stages reflects the influence of axial pressure or confining pressure changes on crack propagation in composite samples. Compared to the initial stress stage, the non-uniformity of AE signals increases in the residual stress stage, and the proportion of large signals becomes more prominent, signifying a complex micro-fracture process in the composite samples.

Multi-modal Modality-masked Diffusion Network for Brain MRI Synthesis with Random Modality Missing.

Synthesis of unavailable imaging modalities from available ones can generate modality-specific complementary information and enable multi-modality based medical images diagnosis or treatment. Existing generative methods for medical image synthesis are usually based on cross-modal translation between acquired and missing modalities. These methods are usually dedicated to specific missing modality and perform synthesis in one shot, which cannot deal with varying number of missing modalities flexibly and construct the mapping across modalities effectively. To address the above issues, in this paper, we propose a unified Multi-modal Modality-masked Diffusion Network (M2DN), tackling multi-modal synthesis from the perspective of "progressive whole-modality inpainting", instead of "cross-modal translation". Specifically, our M2DN considers the missing modalities as random noise and takes all the modalities as a unity in each reverse diffusion step. The proposed joint synthesis scheme performs synthesis for the missing modalities and self-reconstruction for the available ones, which not only enables synthesis for arbitrary missing scenarios, but also facilitates the construction of common latent space and enhances the model representation ability. Besides, we introduce a modality-mask scheme to encode availability status of each incoming modality explicitly in a binary mask, which is adopted as condition for the diffusion model to further enhance the synthesis performance of our M2DN for arbitrary missing scenarios. We carry out experiments on two public brain MRI datasets for synthesis and downstream segmentation tasks. Experimental results demonstrate that our M2DN outperforms the state-of-the-art models significantly and shows great generalizability for arbitrary missing modalities.

Head to head comparison of 68Ga-DOTA-FAPI-04 vs 18F-FDG PET/CT in the evaluation of primary extrapulmonary tumors in the chest.

OBJECTIVE: We conducted a prospective study using 18F-flurodeoxyglucose (18F-FDG) and 68Ga-DOTA-FAPI-04 (fibroblast-activation protein inhibitor, 68Ga-FAPI) PET/CT to diagnose, differentiate, and stage primary extrapulmonary tumors of the thorax. METHODS: Fifty-four participants were undergoing 18F-FDG and 68Ga-FAPI PET/CT and divided into the benign, intermediate, and malignant based on pathology. The maximum standardized uptake value (SUVmax), the tumor-to-blood pool ratio, and tumor-to-liver ratio were compared for primary tumors, lymph nodes, and metastases between the two modalities by two independent samples t tests. One-way ANOVA was used to compare the uptake of 18F-FDG or 68Ga-FAPI among the three groups. RESULTS: Fifty-four participants were confirmed to have 71 primary lesions, 56 metastatic lymph nodes, and 43 metastatic lesions. 18F-FDG PET/CT could both effectively distinguish malignant lesions from non-malignant lesions, accuracies of 87.32% (p < 0.001). 68Ga-FAPI PET/CT effectively differentiated benign lesions from the non-benign, accuracy being 91.55% (p < 0.001). The accuracies of 18F-FDG and 68Ga-FAPI for detecting lymph node metastasis were 77.22% (61/79) and 87.34% (69/79) (p = 0.096). The uptake of 68Ga-FAPI in metastatic lymph nodes was significantly higher than that of the nonmetastatic (p < 0.001). The detection rate of 68Ga-FAPI PET/CT for metastatic lesions was significantly higher than that of 18F-FDG, 100% (43/43) vs. 53.49% (23/43) (p < 0.001). Compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT changed the treatment strategy of 7.4% (4/54) participants. CONCLUSION: 68Ga-FAPI PET/CT is valuable in the diagnosis and differentiation of primary extrapulmonary tumors and superior to 18F-FDG PET/CT for evaluating lymph node and distant metastasis. CLINICAL RELEVANCE STATEMENT: The application of 68Ga-FAPI PET/CT in primary extrapulmonary chest tumors is valuable, which is reflected in diagnosis, differentiation and exploration of lymph node metastasis and distant metastasis. KEY POINTS: • 68Ga-FAPI PET/CT is valuable in the diagnosis, differentiation, and staging of primary extrapulmonary tumors. • 68Ga-FAPI PET/CT is superior to 18 F-FDG PET/CT for evaluating lymph node and distant metastasis.

Somatostatin Receptor Imaging in Mice with Difference Positive Rate of SSTR2.

INTRODUCTION: Imaging with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 was performed to analyze differences among the three probes, and to analyze the correlation between the image and pathology parameters. METHOD: Tumor bearing mice with different positive rates of somatostatin receptor II (SSTR2) were established with HEK293-SSTR2 and HEK293 cells, and imaging was performed on the same mouse with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 at 20, 60 and 120 min. The image parameters were obtained, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), standard deviation of SUVmean (SD), tumor volume and coefficient of variation (CoV). Immunohistochemistry of the tumor was performed after imaging to obtain positive rate of SSTR2. Statistical analysis was performed to analyze the differences among the three imaging techniques and the correlations between the relative imaging parameter and immunohistochemistry (IHC). RESULT: The SUVmax of [18F]AlF-NOTA-JR11 at 20 and 60 min was higher than that of [68Ga]Ga-DOTA-TATE (P=0.0015, 0.0035) and [68Ga]Ga-DOTA-JR11 (P=0.033, 0.019), and no significant difference was found in the other groups (P>0.05). There was a significant positive correlation between the positive rate and SUVmean of tumors with three tracers (P<0.05). However, a significant negative correlation between the positive rate and CoV was found only in the [68Ga]Ga-DOTA-TATE group at 60 min and 120 min (P=0.048, 0.026). CONCLUSION: [18F]AlF-NOTA-JR11 is more suitable for SSTR imaging within an hour than other two tracers. SUVmean of whole tumor can become an indicator for evaluating the positive rate of IHC, and the higher SUVmean of three tracers means a higher positive rate. However, the CoV is not applicable to the two antagonist tracers for evaluating the positive rate.

Study on the correlation between gene polymorphisms of adiponectin and resistin levels and abdominal aortic aneurysm.

OBJECTIVES: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and -420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. METHOD: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and -420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. RESULTS: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of -420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of -420C>G polymorphism were found to be associated with an increased risk and progression of AAA. CONCLUSIONS: The -420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

Background-Aware Classification Activation Map for Weakly Supervised Object Localization.

Weakly supervised object localization (WSOL) relaxes the requirement of dense annotations for object localization by using image-level annotation to supervise the learning process. However, most WSOL methods only focus on forcing the object classifier to produce high activation score on object parts without considering the influence of background locations, causing excessive background activations and ill-pose background score searching. Based on this point, our work proposes a novel mechanism called the background-aware classification activation map (B-CAM) to add background awareness for WSOL training. Besides aggregating an object image-level feature for supervision, our B-CAM produces an additional background image-level feature to represent the pure-background sample. This additional feature can provide background cues for the object classifier to suppress the background activations on object localization maps. Moreover, our B-CAM also trained a background classifier with image-level annotation to produce adaptive background scores when determining the binary localization mask. Experiments indicate the effectiveness of the proposed B-CAM on four different types of WSOL benchmarks, including CUB-200, ILSVRC, OpenImages, and VOC2012 datasets.

Superiority of [68Ga]Ga-DOTA-FAPI-04 PET/CT to [18F]FDG PET/CT in the evaluation of thymic epithelial tumours.

PURPOSE: The purpose of this study is to compare the ability of [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial tumours (TETs). METHODS: From April 2021 to November 2022, participants with suspected TETs confirmed by histopathology or follow-up imaging were prospectively analysed. All participants underwent [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. Clinical characteristics, CT features, and metabolic parameters (maximum standardized uptake value [SUVmax] and tumour-to-mediastinum ratio [TMR]) of subjects with different pathological types and stages were compared. The diagnostic capacities of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were compared using receiver operating characteristic (ROC) curves and McNemar's test. RESULTS: Fifty-seven participants were included. [68Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [18F]FDG PET/CT in differentiating thymomas from thymic carcinomas (TCs) (AUC: 0.99 vs. 0.90, P = 0.02). Logistic regression revealed that SUVmax-FAPI (P = 0.04) was a significant predictive factor for TCs. SUVmax-FAPI and TMR-FAPI showed an excellent ability to differentiate low-risk thymomas (types A, AB, and B1), high-risk thymomas (types B2 and B3), and TCs (both P < 0.001). In thymomas, only SUVmax-FAPI (P < 0.001), TMR-FAPI (P < 0.001), and nonsmooth edges (P = 0.02) were significantly higher in the advanced-stage (Masaoka-Koga [MK] stage III/IV) group than in the early-stage group (MK stage I/II). Compared with [18F]FDG PET/CT, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed significantly higher specificity (67% [46 of 69] vs. 93% [64 of 69], P < 0.001) in the detection of lymph node metastases and higher sensitivity (49% [19 of 39] vs. 97% [38 of 39], P < 0.001) in evaluating distant metastases. Both SUVmax-FAPI and TMR-FAPI were correlated with FAP expression (both r = 0.843, P < 0.001). CONCLUSION: [68Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [18F]FDG PET/CT in evaluating the World Health Organization (WHO) classification, MK staging, and metastatic status of TETs. TRIAL REGISTRATION: ChiCTR2000038080, registration date 2020-09-09, https://www.chictr.org.cn/com/25/showproj.aspx?proj=61192.

Preparation and Application of a Bioorganic Nanoparticle-Enhanced PDL1-Targeted Small-Molecule Probe.

Programmed death ligand 1 (PDL1) is a specific molecular target for the diagnosis and immunotherapy of solid tumors. PET imaging can be used for noninvasive assessments of PDL1 expression in tumors to aid in therapy selection. The most frequently reported small-molecule radiotracer of PDL1 is limited by low imaging specificity, short residence time, and singular functionality. Here, we combined a biocompatible melanin nanoprobe with the PDL1-binding peptide WL12 to construct a novel radiotracer, 124I-WPMN, to enhance PDL1 targeting. The radiochemical purity of 124I-WPMN was >95%, and uptake in A549PDL1 cells was 1.49 ± 0.08% at 2 h. The uptake was blocked by WL12 (0.39 ± 0.03%, P < 0.0001). This novel radiotracer showed a higher affinity for PDL1 (Kd = 18.5 nM) than 68Ga-NOTA-WL12 (Kd = 24.0 nM). Micro-PET/CT imaging demonstrated specific uptake and a high signal-to-noise ratio in an A549PDL1 xenograft mouse model with a tumor-to-muscle ratio of 27.31 ± 7.03 at 2 h. The levels increased or remained steady for more than 72 h, and tumor uptake was significantly higher than 68Ga-NOTA-WL12, at 6.08 ± 0.62 at 2 h. Prolonged retention of 124I-WPMN makes it possible to conduct PET/MRI imaging over long periods and to perform various imaging techniques. A clear advantage of 124I-WPMN over 68Ga-NOTA-WL12 was observed for PDL1-targeted PET imaging after nanoparticle modification, supporting the utility of 124I-WPMN PET imaging as an effective diagnostic tool for optimizing PDL1-targeted therapies.

Enhanced Proliferation of Visualizable Mesenchymal Stem Cell-Platelet Hybrid Cell for Versatile Intracerebral Hemorrhage Treatment.

The intrinsic features and functions of platelets and mesenchymal stem cells (MSCs) indicate their great potential in the treatment of intracerebral hemorrhage (ICH). However, neither of them can completely overcome ICH because of the stealth process and the complex pathology of ICH. Here, we fabricate hybrid cells for versatile and highly efficient ICH therapy by fusing MSCs with platelets and loading with lysophosphatidic acid-modified PbS quantum dots (LPA-QDs). The obtained LPA-QDs@FCs (FCs = fusion cells) not only inherit the capabilities of both platelets and MSCs but also exhibit clearly enhanced proliferation activated by LPA. After systemic administration, many proliferating LPA-QDs@FCs rapidly accumulate in ICH areas for responding to the vascular damage and inflammation and then efficiently prevent both the primary and secondary injuries of ICH but with no obvious side effects. Moreover, the treatment process can be tracked by near-infrared II fluorescence imaging with highly spatiotemporal resolution, providing a promising solution for ICH therapy.

Study on the dust migration law and a spray dust suppression scheme in transportation roadway.

To solve the problem of excessive dust concentration in the belt transportation roadway of the mine. Numerical simulations were used to study the dust migration in the belt transportation roadway under 1.5 m/s ventilation conditions. The simulation results show the process of dust ejection from the inflow chute to contamination of the whole belt transportation roadway, and the spatial distribution of dust velocity. A comprehensive dust reduction scheme of "central suppression and bilateral splitting" was designed according to the dust distribution, with simultaneous control of the infeed chute and the roadway. In practical application, pneumatic spraying greatly reduces the amount of dust in the guide chute. The misting screen has a significant effect on dust collection and segregation. The solution effectively controls the dust in the space of 20 m on both sides of the transfer point, and the dust removal efficiency reaches more than 90%.

Harmonization of standard uptake values across different positron emission tomography/computed tomography systems and different reconstruction algorithms: validation in oncology patients.

BACKGROUND: EQ.PET is a software package that overcomes the reconstruction-dependent variation of standard uptake values (SUV). In this study, we validated the use of EQ.PET for harmonizing SUVs between different positron emission tomography/computed tomography (PET/CT) systems and reconstruction algorithms. METHODS: In this retrospective study, 49 patients with various cancers were scanned on a Biograph mCT (mCT) or Gemini TF 16 (Gemini) after [18F]FDG injections. Three groups of patient data were collected: Group 1, patients scanned on mCT or Gemini with data reconstructed using two parameters; Group 2, patients scanned twice on different PET scanners (interval between two scans, 68.9 ± 41.4 days); and Group 3, patients scanned twice using mCT with data reconstructed using different algorithms (interval between two scans, 109.5 ± 60.6 days). The SUVs of the lesions and background were measured, and the tumor-to-background ratios (TBRs) were calculated. In addition, the consistency between the two reconstruction algorithms and confounding factors were evaluated. RESULTS: In Group 1, the consistency of SUV and TBR between different reconstruction algorithms improved when the EQ.PET filter was applied. In Group 2, by comparing ΔSUV, ΔSUV%, ΔTBR, and ΔTBR% with and without the EQ.PET, the results showed significant differences (P < 0.05). In Group 3, Bland-Altman analysis of ΔSUV with EQ.PET showed an improved consistency relative to that without EQ.PET. CONCLUSIONS: EQ.PET is an efficient tool to harmonize SUVs and TBRs across different reconstruction algorithms. Patients could benefit from the harmonized SUV, ΔSUV, and ΔSUV% for therapy responses and follow-up evaluations.

Study on an Animal Model of Seawater Immersion Injury Following Hemorrhagic Shock.

INTRODUCTION: To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS). METHODS: Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded. RESULTS: After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05. CONCLUSIONS: The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock.

Cymbaria daurica L.: A Mongolian herbal medicine for treating eczema via natural killer cell-mediated cytotoxicity pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbaria daurica L. (C. daurica) is a perennial herb known commonly as "Xinba" (Chinese) and "Kanba-Arong" (Mongolian). In Mongolia, it is used as a traditional medicine to treat eczema and other skin diseases due to its anti-swelling, anti-inflammatory, anti-hemorrhagic, and anti-itching properties. However, the potential mechanism of action for eczema treatment has not been reported. AIM OF THE STUDY: To investigate the effect of C. daurica on 1-chloro-2,4-dinitrobenzene (DNCB)-induced eczema in rats and the associated action mechanism. MATERIALS AND METHODS: Qualitative analysis of C. daurica was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on information obtained from compound identification and relevant literature, the possible targets of C. daurica against eczema were analyzed using network pharmacology and molecular docking methods. The DNCB-induced eczema rat models were treated with different dosages of C. daurica extract (10, 50, and 250 mg/mL per day), and the therapeutic effects subsequently evaluated based on the degree of skin inflammation, spleen index, and hematoxylin and eosin staining (H&E staining). Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were used to analyze the relevant target effects. The C. daurica mechanism of action on eczema was verified by animal experiments. High-performance liquid chromatography (HPLC) was carried out to determine the content of active ingredients in C. daurica. In addition, the physicochemical properties of the extract were evaluated. RESULTS: Our analysis of the 173 targets included in the protein-protein interaction (PPI) network identified tumor necrosis factor (TNF) and interleukin 2 (IL-2) as key targets involved in the treatment of eczema with C. daurica extract. Furthermore, the 173 targets were associated with the natural killer cell-mediated cytotoxicity pathway. Our results showed that C. daurica significantly reduced IL-2 and TNF-α serum levels in eczema rat models (P < 0.0001); thus, playing an important role in the anti-inflammatory response. Furthermore, according to the p-value, RT-qPCR and western blotting showed that the expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Vav guanine nucleotide exchange factor (Vav), and growth factor receptor-bound protein 2 (Grb2) changed in the skin of the eczema model rats after treatment with the C. daurica extract. CONCLUSION: Our study confirms that C. daurica can inhibit SHP-1, Vav, and Grb2 expression; thereby, inhibiting the natural killer cell-mediated cytotoxicity pathway. These results provide insight into the mechanism of C. daurica in treating eczema.

A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics.

Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-ß signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.

Predictive Value of 18 F-FDG PET/MRI for Pleural Invasion in Solid and Subsolid Lung Adenocarcinomas Smaller Than 3 cm.

BACKGROUND: Positron emission tomography (PET)/MRI combines the characteristics of metabolism imaging and high soft tissue resolution, and could provide high diagnostic efficacy for assessment of pleural invasion (PI) of lung cancer. PURPOSE: To investigate the application of 18 F-fluorodeoxyglucose (FDG) PET/MRI for predicting PI of lung cancer with the maximum diameter ≤3 cm. STUDY TYPE: Prospective. POPULATION: A total of 44 patients with non-small cell lung cancer (NSCLC), age from 39 to 79 years old, including 19 (56.82%) females. FIELD STRENGTH/SEQUENCE: A 3-T, hybrid PET/MRI including axial fast spin echo respiratory-triggered T2 fat-suppressed imaging (T2FS) and echo planar imaging diffusion-weighted imaging (DWI). ASSESSMENT: The maximum standardized uptake value (SUVmax) of all lesions was measured on PET images. Localized effusion outside the contact between the nodules and the pleura on T2FS and signal at the contact between the nodules and the pleura on DWI were evaluated by experienced physicians through visual assessment of the MRI sequences. STATISTICAL TESTS: Three models (models 1-3) were developed, incorporating CT, CT and PET, PET and MRI features, and Lasso regression was used in feature selection. The receiver operating characteristic (ROC) curve for PI diagnosis was visualized for each model, and the area under the curve (AUC) was calculated. The DeLong test was used to compare the different AUCs. A P value < 0.05 was considered statistically significant. RESULTS: The AUC of models 1-3 was 0.762, 0.829, and 0.915, respectively. The DeLong test showed a statistically significant difference between the AUCs of model 1 vs. model 3, while the differences between the AUCs of model 1 vs. model 2 (P = 0.253) and model 2 vs. model 3 (P = 0.075) were not statistically significant. DATA CONCLUSION: 18 F-FDG PET/MRI might show high predictive value for lung adenocarcinoma smaller than 3 cm with PI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

High in-vivo stability in preclinical and first-in-human experiments with [18F]AlF-RESCA-MIRC213: a 18F-labeled nanobody as PET radiotracer for diagnosis of HER2-positive cancers.

PURPOSE: [18F]AlF-RESCA was introduced as a core particularly useful for 18F-labeling of heat-sensitive biomolecules. However, no translational studies have been reported up to now. Herein, we reported the first-in-human evaluation of an 18F-labeled anti-HER2 nanobody MIRC213 as a PET radiotracer for imaging HER2-positive cancers. METHODS: MIRC213 was produced by E. coli and conjugated with ( ±)-H3RESCA-Mal. [18F]AlF-RESCA-MIRC213 was prepared at room temperature. Its radiochemical purity and stability of were determined by radio-HPLC with the size-exclusion chromatographic column. Cell uptake was performed in NCI-N87 (HER2 +) and MCF-7 (HER2-) cells and the cell-binding affinity was verified in SK-OV-3 (HER2 +) cells. Small-animal PET/CT was performed using SK-OV-3, NCI-N87, and MCF-7 tumor-bearing mice at 30 min, 1 h, and 2 h post-injection. For blocking experiment, excess MIRC213 was co-injected with radiotracer. Biodistribution were performed on SKOV-3 and MCF-7 tumor-bearing mice at 2 h post-injection. For clinical study, PET/CT images were acquired at 2 h and 4 h after injection of [18F]AlF-RESCA-MIRC213 (1.85-3.7 MBq/kg) in six breast cancer patients (3 HER2-positive and 3 HER2-negative). All patients underwent [18F]-FDG PET/CT within a week for tissue selection purpose. Distribution and dosimetry were calculated. Standardized uptake values (SUV) were measured in tumors and normal organs. RESULTS: MIRC213 was produced with > 95% purity and modified with RESCA to obtain RESCA-MIRC213. [18F]AlF-RESCA-MIRC213 was prepared within 20 min at room temperature with the radiochemical yield of 50.48 ± 7.6% and radiochemical purity of > 98% (n > 10), and remained stable in both PBS (88%) and 5% HSA (92%) after 6 h. The 2 h cellular uptake of [18F]AlF-RESCA-MIRC213 in NCI-N87 cells was 11.22 ± 0.60 AD%/105 cells. Its binding affinity Kd value was determined to be 1.23 ± 0.58 nM. Small-animal PET/CT with [18F]AlF-RESCA-MIRC213 can clearly differentiate SK-OV-3 and NCI-N87 tumors from MCF-7 tumors and background with a high uptake of 4.73 ± 1.18 ID%/g and substantially reduced to 1.70 ± 0.13 ID%/g for the blocking group (p < 0.05) in SK-OV-3 tumors at 2 h post-injection. No significant bone radioactivity was seen in the tumor-bearing animals. In all six breast cancer patients, there was no adverse reaction during study. The uptake of [18F]AlF-RESCA-MIRC213 was mainly in lacrimal gland, parotid gland, submandibular gland, thyroid gland, gallbladder, kidneys, liver, and intestines. There was no significant bone radioactivity accumulation in cancer patients. [18F]AlF-RESCA-MIRC213 had significantly higher tumor uptake in lesions from HER2-positive patients than that lesions from HER2-negative patients (SUVmax of 3.62 ± 1.56 vs. 1.41 ± 0.41, p = 0.0012) at 2 h post-injection. The kidneys received the highest radiation dose of 2.42 × 10-1 mGy/MBq, and the effective dose was 1.56 × 10-2 mSv/MBq. CONCLUSIONS: [18F]AlF-RESCA-MIRC213 could be prepared with high radiolabeling yield under mild conditions. [18F]AlF-RESCA-MIRC213 has relatively high stability both in vitro and in vivo. The results from clinical transformation suggest that [18F]AlF-RESCA-MIRC213 PET/CT is a safe procedure with favorable pharmacokinetics and dosimetry profile, and it is a promising new PET radiotracer for noninvasive diagnosis of HER2-positive cancers.

SGLSA: Sphygmus gated laser speckle angiography for microcirculation hemodynamics imaging.

Hemodynamics imaging of the retinal microcirculation has been demonstrated to be potential access to evaluating ophthalmic diseases, cardio-cerebrovascular diseases, and metabolic diseases. However, existing structural and functional imaging techniques are insufficient in spatial or temporal resolution. The sphygmus gated laser speckle angiography (SGLSA) is proposed for structural and functional imaging with high spatiotemporal resolution. Compared with classic LSCI algorithms, SGLSA presents a much clearer perfusion image and higher signal-to-noise ratio pulsatility. The SGLSA algorithm also shows better performance on patients than traditional LSCI methods. The high spatiotemporal resolution provided by the SGLSA algorithm greatly enhances the ability of retinal microcirculation analysis, which makes up for the deficiency of the LSCI technology, and attaches great significance to retinal hemodynamic imaging, biomarker research, and clinical diagnosis.

Study on the correlation between gene polymorphisms of adiponectin and resistin levels and abdominal aortic aneurysm

Abstract Objectives: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and −420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. Method: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and −420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. Results: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of −420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of −420C>G polymorphism were found to be associated with an increased risk and progression of AAA. Conclusions: The −420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

Bellidifolin from Gentianella acuta (Michx.) Hulten protects H9c2 cells from hydrogen peroxide-induced injury via the PI3K-Akt signal pathway.

Cardiovascular disease is the most common disease in the world and the first among the causes of human death. Its morbidity and mortality increase annually, but no effective treatment is available. Therefore, new drugs should be developed to treat cardiovascular disease. Gentianella acuta (Michx.) Hulten (G. acuta) is an important Mongolian medicine in China and elicits protective effects on cardiovascular health. In this study, liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the main active ingredients and confirm that bellidifolin was one of the main components for the treatment of ischemic heart disease. Then, rat myocardial (H9c2) cells injury model induced by hydrogen peroxide (H2O2) in vitro was established to verify the effect of bellidifolin on oxidative stress stimulation, including determination of antioxidant enzyme activity and apoptosis. Transcriptome sequencing, qRT-PCR, and western blot were performed to further verify the antioxidant stress mechanism of bellidifolin. Results showed that bellidifolin pretreatment decreased the rate of apoptosis and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), and alanine aminotransferase (ALT). Conversely, it increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in a dose-dependent manner, indicating that bellidifolin caused a protective effect on cardiomyocyte injury. Bellidifolin minimized the H2O2-induced cell injury by activating the PI3K-Akt signal pathway and downregulating glycogen synthase kinase-3ß (GSK-3ß) and p-Akt1/Akt1. Therefore, this work revealed that G. acuta has a good development prospect as an edible medicinal plant in cardiovascular disease. Its bellidifolin component is a potential therapeutic agent for cardiovascular disease induced by oxidative stress damage.