Eudragit L100-coated nintedanib nanocrystals improve oral bioavailability by reducing drug particle size and maintaining drug supersaturation.

The aim of this study was to prepare nintedanib nanocrystals (BIBF-NCs) to lower the solubility of the drug in the stomach, maintain the supersaturation of the drug in the intestine, and improve the oral absorption of nintedanib (BIBF). In this study, BIBF-NCs were prepared by acid solubilization and alkaline precipitation following nano granding method, with a particle size of 290.80 nm and a zeta potential of -49.13 mV. Subsequently, Nintedanib enteric-coated nanocrystals (BIBF-NCs@L100) were obtained by coating with Eudragit L100. The microscopic morphology, crystalline characteristics, stability, and in vitro dissolution of BIBF-NCs and BIBF-NCs@L100 were also studied. In addition, the in vivo pharmacokinetic behaviors of Samples prepared according to the prescription process of commercially available soft capsules (soft capsules), BIBF-NCs, and BIBF-NCs@L100 were further investigated. The results showed that the oral bioavailability of BIBF-NCs and BIBF-NCs@L100 were increased by 1.43 and 2.58 times, compared with that of the soft capsules. BIBF-NCs@L100 effectively reduced the release of BIBF in the formulation in the stomach, allowing more drug to reach the intestine in the form of nanocrystals, maintaining the supersaturation in the intestine, thereby improving the oral bioavailability of the drug.

Use of a radiomics-clinical model based on magnetic diffusion-weighted imaging for preoperative prediction of lymph node metastasis in rectal cancer patients.

Rectal cancer is the eighth most prevalent malignancy worldwide with a 3.2% mortality rate and 3.9% incidence rate. Radiologists still have difficulty in correctly diagnosing lymph node metastases that have been suspected preoperatively. To assess the effectiveness of a model combining clinical and radiomics features for the preoperative prediction of lymph node metastasis in rectal cancer. We retrospectively analyzed data from 104 patients with rectal cancer. All patients were selected as samples for the training (n = 72) and validation cohorts (n = 32). Lymph nodes (LNs) in diffusion-weighted images were analyzed to obtain 842 radiomic characteristics, which were then used to draw the region of interest. Logistic regression, least absolute shrinkage and selection operator, and between-group and within-group correlation analyses were combined to establish the radiomic score (rad-score). Receiver operating characteristic curves were used to estimate the prediction accuracy of the model. A calibration curve was constructed to test the predictive ability of the model. A decision curve analysis was performed to analyze the model's value in clinical application. The area under the curve for the radiomics-clinical, clinical, and radiomics models was 0.856, 0.810, and 0.781, respectively, in the training cohort and 0.880, 0.849, and 0.827, respectively, in the validation cohort. The calibration curve and DCA showed that the radiomics-clinical prediction model had good prediction accuracy, which was higher than that of the other models. The radiomics-clinical model showed a favorable predictive performance for the preoperative prediction of LN metastasis in patients with rectal cancer.

Asymmetry of brain development in adolescent rats studied by 3.0 T magnetic resonance imaging.

To study the developmental patterns of brain structure in adolescent rats based on the registration with the SIGMA template by 3.0T MRI. Forty male Sprague-Dawley rats (180-220 g) were randomly divided into four groups. Rats in the four groups underwent 3.0 T MRI head scans at 7, 11, 15, and 19 weeks of age, respectively. The voxel-based morphological analysis of the rat brain was performed by coregistration with the SIGMA rat brain template. 3.0 T MRI can be used to study the anatomical structure of the rat brain by registration with the SIGMA template The gray matter volume of the bilateral hippocampus and bilateral entorhinal cortex increased significantly in the development of the rat from 7 to 19 weeks of age. In this period, the subtle structure of the rat brain is asymmetrically developed. The rat aged 7-19 weeks has asymmetrical gray matter volume development in the bilateral entorhinal cortex and hippocampus.

Establishment of a Rat Model of Infraorbital Neuroinflammation Under CT Guidance.

INTRODUCTION: The aim is to establish a rat model of infraorbital neuroinflammation with less trauma, stable pain, and a long duration of pain. The pathogenesis of TN is not fully clear. There are various models of TN in rats with different disadvantages, such as damaging the surrounding structures and inaccuracy of location for infraorbital nerve (ION). We aim to establish a rat model of infraorbital neuroinflammation with minimal trauma, a simple operation, and accurate positioning under CT guidance to help us study the pathogenesis of trigeminal neuralgia. METHODS: Thirty-six adult male Sprague Dawley rats (180-220 g) were randomly divided into 2 groups and injected with talc suspension or saline through the infraorbital foramen (IOF) under CT guidance. Mechanical thresholds were measured in the right ION innervation region of 24 rats over 12 postoperative weeks. At 4 weeks, 8 weeks, and 12 weeks after the operation, the inflammatory involvement of the surgical area was evaluated by MRI, and neuropathy was observed using a transmission electron microscope (TEM). RESULTS: The talc group had a significant decrease in the mechanical threshold at 3 days after surgery that continued until 12 weeks post-operation, and the talc group had a significantly lower mechanical threshold than the saline group 10 weeks post-operation. The talc group had significantly impaired trigeminal nerve (TGN) myelin after 8 weeks post-operation. CONCLUSION: The rat model of infraorbital neuroinflammation established by CT-guided injection of talc into the IOF is a simple operation that results in less trauma, stable pain, and a long duration of pain. Moreover, infraorbital neuroinflammation in peripheral branches of the TGN can cause demyelination of the TGN in the intracranial segment.

Preoperative Radiomics Nomogram Based on CT Image Predicts Recurrence-Free Survival After Surgical Resection of Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To construct preoperative models based on CT radiomics, radiologic and clinical features to predict recurrence-free survival (RFS) after liver resection (LR) of BCLC 0 to B stage hepatocellular carcinoma (HCC) and to classify the prognosis. MATERIALS AND METHODS: This study retrospectively analyzed 161 HCC patients who underwent radical LR. Two methods, the least absolute shrinkage and selection operator and random survival forest analysis, were performed for radiomics signature (RS) construction. Univariate and multivariate stepwise Cox regression analyses were performed to establish a combined nomogram (RCN) of RS and clinical parameters and a clinical nomogram (CN). The performance of the models was assessed comprehensively using Harrell's concordance index (C-index), the calibration curve, and decision curve analysis. The discrimination accuracy of the models was compared using integrated discrimination improvement index (IDI). The risk stratification effect was assessed with Kaplan-Meier survival analysis and subgroup analysis. RESULTS: The RCN achieved a C-index of 0.792/0.758 in the training/validation set, which was higher than the CN, RS, and BCLC stage system. The discriminatory accuracy of the RCN was improved when compared to the CN, RS, and BCLC staging systems (IDI > 0). Decision curve analysis reflected the clinical net benefit of the RCN. The RCN allows risk stratification of patients in different clinical subgroups. CONCLUSION: The integrated model combining RS and clinical factors can more effectively predict RFS after LR of BCLC 0 to B stage HCC patients and can effectively stratify the prognostic risk.

Experience Mode of Digital Media Art under Virtual Reality Technology.

With the progress of the country's comprehensive strength and scientific strength, the development of science and technology has brought tremendous changes to people's lives and at the same time brought information dissemination and media methods to a new stage. This article integrates VR technology into your digital media art experience. This combination not only reduces the distance between the experience and the art but also allows the experiencers to better understand what the artist wants to convey in the artwork. Virtual reality technologies and experts have shifted from bystanders to participants and experiencers. This is a brand new experience. It dispels our previous experience based on visual experience and forms a new form of experience. The final results of the study showed that the scores of the three classes of cognitive experience were 4.8, 4.6, and 4.7, with an average score of 4.7. With a full score of 5, the scores in the three dimensions are very high, indicating that this digital media art interactive experience design has brought students a good sensory experience, interactive experience, and cognitive experience.

Recent Advances of Magnetic Resonance Neuroimaging in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a disease of unclear pathogenesis. It has a low incidence and is not fatal, but it can cause afflicted patients' depression or suicide. In the past, neurovascular compression was considered to be the main cause of TN, but recent studies have found that neurovascular contact is also common in asymptomatic patients and the asymptomatic side in symptomatic patients. This indicates that the neurovascular contact is not, or is only to a lesser extent, a factor in the development of TN. Thus, the study of the peripheral branches of the trigeminal nerve is necessary to understand the etiology of TN. With the development of imaging technology and the emergence of various imaging modalities, it is possible to study the etiology of TN and the pathological changes of related structures by magnetic resonance neuroimaging. This article reviews the recent advances in magnetic resonance neuroimaging of the trigeminal nerve.

Novel insights into the role of Clostridium novyi-NT related combination bacteriolytic therapy in solid tumors.

Several solid tumors (for example leiomyosarcoma, melanoma and hepatocellular carcinoma) possess areas of hypoxia, which underlies one of the primary reasons of failure of conventional anticancer therapies. The areas of poor vascularization are insensitive to radiotherapy and chemotherapeutic drugs. Conversely, the hypoxic regions of tumors provide an ideal environment for anaerobic bacteria. The attenuated anaerobic bacterium, Clostridium novyi-NT (C. novyi-NT), is highly sensitive to oxygen and can target the destruction of hypoxic and necrotic areas of tumors, inducing oncolysis and characteristics indicative of an immune response. Theoretically, chemotherapy, radiotherapy and immunotherapy combined with bacterial therapy can be used as a novel means of treating solid tumors, promoting tumor regression and inhibiting metastasis formation with a notable beneficial effect. The present review discusses the molecular mechanisms of combined bacteriolytic therapy, predominantly focusing on C. novyi-NT, and summarizes the findings of previous studies on experimental animal models, including its efficacy and safety via different drug delivery routes. This strategy has great potential to overcome the limitations of conventional cancer therapy, resulting in improved treatments, and thus potentially improved outcomes for patients.

Effects of dietary coated-oleum cinnamomi supplementation on the immunity and intestinal integrity of broiler chickens.

Oleum cinnamomi (OCM) is increasingly used as a feed additive in animal diets. The aim of this study was to investigate the effects of dietary supplementation with coated-OCM (cOCM) on the immunity and intestinal integrity of broiler chickens. A total of 396 one-day-old chicks were randomly assigned into six groups. The basal diets were supplemented with 50 mg/kg of flavomycin (positive control) as well as 0 (control), 50, 100, 200, and 300 mg/kg of cOCM. Compared with the control, both positive control and cOCM treatments did not improve the growth performance. Serum immunoglobulin (Ig) Y levels were decreased by flavomycin and 50 mg/kg of cOCM treatments (p < 0.05). Dietary cOCM decreased ileal secretory IgA contents at d 21 and commonly down-regulated duodenal and ileal mRNA expression of interleukin (IL)-1ß and IL-8 at d 42 (p < 0.05). The 300 mg/kg of cOCM increased jejunal ratio of villus height to crypt depth and upregulated intestinal claudin-1 expression (p < 0.05). Jejunal (at d 21) and duodenal (at d 42) mucin-2 expression was up and downregulated by both 50 and 300 mg/kg of cOCM, respectively (p < 0.05). In conclusion, dietary cOCM addition helped to maintain noninflammatory states of humoral and mucosal immunity, and improved the intestinal integrity of broiler chickens.

Two Lactobacillus Species Inhibit the Growth and α-Toxin Production of Clostridium perfringens and Induced Proinflammatory Factors in Chicken Intestinal Epithelial Cells in Vitro.

Clostridium perfringens is the causative pathogen of avian necrotic enteritis. Lactobacillus spp. are well-characterized probiotics with anti-microbial and immune-modulatory activities. In the present study, we investigated the effects of L. acidophilus and L. fermentum on the growth, α-toxin production and inflammatory responses of C. perfringens. In in vitro culture experiments, both lactobacilli inhibited the growth of C. perfringens (P < 0.01), accompanied with a decrease in pH (P < 0.01). Supernatants from lactobacilli cultures also suppressed the growth of C. perfringens during 24 h of incubation (P < 0.01), but this inhibitory effect disappeared after 48 h. Both lactobacilli decreased the α-toxin production of C. perfringens (P < 0.01) without influencing its biomass, and even degraded the established α-toxin (P < 0.01). Lower environmental pH reduced the α-toxin production as well (P < 0.01). Preincubation with L. acidophilus decreased the attachment of C. perfringens to cells (P < 0.01) with the cell cytotoxicity being unaffected. Both lactobacilli pretreatment reduced the up-regulation of proinflammatory factors, peptidoglycan (PGN) receptors and nuclear factor kappa B (NF-κB) p65 in C. perfringens-challenged chicken intestinal epithelial cells (P < 0.05). In conclusion, L. acidophilus and L. fermentum inhibited the pathological effects of C. perfringens in vitro conditions.